Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles.
Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task.
Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles.
Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype.
ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present.
Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype.
Yes
C57BL/6J
Tg(Prnp-ITM2B*)6Jckr and Tg(Prnp-ITM2B*)7Jckr
Adult mice fail to gain weight with age. Alopecia. Kyphosis.
Homozygous animals are viable, normal in size, fertile, and do not display any gross physical or behavioral abnormalities up to 22 months of age. No impairments in axonal outgrowth of olfactory neurons following bulbectomy.
2-fold higher level of steady state APOE in brain and higher APOE in serum compared with APOE3 and APOE4 KI animals. Highest levels of serum cholesterol and triglycerides after a 6hr fast.
Characteristics of type III hyperlipoproteinemia. Plasma cholesterol and triglyceride levels 2-3x higher than APOE3 mice. Impaired clearance of very-low-density lipoprotein (VLDL) particles. Atherosclerotic plaques.
On a standard diet, homozygous mice have normal cholesterol and triglyceride levels, but are more susceptible than wild-type animals to diet-induced atherosclerosis.
Human ApoE is detectable in serum and astrocytes. Compared to mice with knock-in of APOE2 or APOE3, APOE4 mice had the lowest serum cholesterol after a 6 hour fast.
Viable; healthy. Undetectable ApoE protein in plasma. Plasma cholesterol 5x higher than wild-type. Artherosclerotic lesions which progress to occlusions of coronary artery by 8 months.
Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages.
Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages.
Yes
C57BL/6
B6.Cg-Tg(Thy1-APP)3Somm/J
Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months.
Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques.
Short-term memory deficits apparent by 3-4 months as measured by the Y maze.
Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons.
Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates.
Yes
The PS1KI line was established in 129SV and backcrossed >7 times to C57BL/6 background. The PS1KI were bred with APPSL mice on a C57BL background (two rounds) to obtain a homozygote PS1KI and heterozygote APP.
Viable and fertile. 6 month-old animals develop decreases in body weight, and a spinal deformity (kyphosis) is common. Impaired neurogenesis.
No neuropathology up to age 29 months; however, pathology reminiscent of inclusion body myopathy observed at 6-12 months: Aβ-immunoreactive deposits in skeletal muscle fibers. Muscle fibers with Aβ-immunoreactive deposits increased with age and also became vacuolated.
Hypoactivity. The acquisition of place learning in the Morris water maze task was impaired.
No
C57BL/6 x DBA/2
Higher cytochrome oxidase activity in thalamic nuclei. High levels of Aβ peptides in the plasma.
Available through Ken-ichiro Fukuchi, University of Illinois College of Medicine at Peoria
Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease
Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed.
Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus.
Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP.
Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.
Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze.
Yes
C57BL/6
Apptm2.1Tcs/Apptm2.1Tcs
No overexpression of APP. Generates wild-type levels of AICD.
Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.
Memory impairment by 6 months as measured by the Y maze.
Yes
C57BL/6
Apptm3.1Tcs/Apptm3.1Tcs
No overexpression of APP. Wild-type levels of AICD.
Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months.
Yes
C57BL/6J
B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr
Aβ42 concentration in CSF decreases with age, with a 50% reduction by 6 months and an 80% reduction by 18 months. Aβ40 concentration also decreases, but less robustly (45% by 18 months). CSF concentration of total tau increases, starting at 6 months, and reaches a 5-fold increase by 18 months.
Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed.
Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus.
Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition.
Yes
APPsw mice on C57BL/6; Pdgfrβ+/- mice on 129S1/SvlmJ.
Progressive loss of pericytes due to reduced Pdgfrβ signaling. Early and progressive blood brain barrier breakdown, indicated by cerebral accumulation of IgG. Reduced microvascular circulation, indicated by reduced capillary length.
Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone.
Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks.
Yes
C57BL/6J; C57BL/6N
B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
Decreased neuropeptide Y staining throughout the hippocampus, particularly in the CA3 region and subiculum.
Amyloid plaques by 17-18 months in the neocortex and hippocampus with detection of 5-10 fold more Aβ40 than Aβ42. Plaque burden significantly lower than in the double transgenic PS2APP. Lower levels of insoluble Aβ40 and Aβ42 than the PS2APP mouse at 16-18 months.
By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months.
Unknown.
Yes
(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
B6.129-Tg(APPSw)40Btla/Mmjax
Increased mortality in young homozygous animals, especially females. At 3-4 months mice maintained on the C57BL/6J background exhibit spontaneous seizure-like activity as measured by EEG and are more susceptible to kainic acid-induced seizures.
Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus.
Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task.
Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers.
Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months.
Yes
Line C3-3: C57BL/6J; Line S-9: hybrid strain C3H/HeJ;C57BL/6J) backcrossed to C57BL/6J
B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J
At 19 months, small but significant decrease in acetylcholinesterase activity in the hippocampus and choline acetyl transferase (ChAT) in the hippocampus and cortex.
Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity.
Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing).
Yes
C57BL/6;C3H
B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Kinked tail phenotype that is believed to be due to genetic background.
The Jackson Lab; available through the JAX MMRRC Stock# 034829 (formerly Jackson Lab Stock # 004462); Live
Increased Aβ42 in the cortex and hippocampus of 12 month old mice, but no plaques. Increased tau phosphorylation and TUNEL-stained nuclei relative to control mice.
In water maze tests, 12 month old mice had longer escape latencies than age-matched control mice.
No
Origin: C57BL/6 x DBA/2
Metallothionein expression was increased in brain astrocytes and was thought to attenuate Aβ-induced neurotoxicity. Increased Cox-2 and caspase-3 compared to age-matched control mice.
Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.
At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.
Yes
Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice
Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.
From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression.
Yes
Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N
Tg(Thy1-APPLon)2Vln/0
Increased mortality (72% by day 180). Increased incidence of seizures.
Available through the KU Leuven Research and Development Office; the CRO reMYND offers research services with this line.
Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology.
From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression.
Yes
Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N
Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-PSEN1*A246E)2Vln/0
The CRO reMYND offers research services with this line.
Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.
At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.
Yes
Inbred C57BL/6
Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus.
At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.
Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.
Yes
Origin: B6D2 F1
Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI.
Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches.
Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months.
Yes
Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6
B6;CB-Tg(Thy1-PSEN1*M146V/Thy1-APP*swe)10Arte
Good breeding capabilities and no premature death.
Hypomyelination in the hippocampus and cerebral cortex, but normal axonal development.
Increased thermal pain sensitivity as measured by a hot plate test. Decreased grip strength.
No
C57BL/6J
B6.129-Bace1tm1Pcw/J
Homozygous mice are viable, fertile, normal in size. No BACE1 protein is detected by Western blot. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs).
Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss.
On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.
Yes
B6C3, backcrossed to C57BL/6J to generate congenic strain
Premature differentiation of neural progenitor cells results in reduced cells and neurons. 45 percent of late-born neurons fail to migrate to their appropriate positions in the superficial cortical layers.
Gross behavior deficits.
No
C57BL6/129
fPS1/fPS1Δ;Nestin-Cre (PS1 cKO)
Mice are small. Premature death at 2-3 months of age.
Decreased levels of full-length mature APP and increased levels of C99 and C89. Human BACE mRNA 4x higher than endogenous murine BACE. Highest expression of human BACE protein in cortex and hippocampus, lowest in cerebellum.
Available through Material Transfer Management at Novartis
Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss.
Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009).
Yes
The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells that were subsequently injected into C57BL/6 blastocysts. The transgenic allele was generated in embryos derived from a cross between Swiss Webster and B6D2F1. Mice containing both alleles were back-crossed to C57BL/6 mice .
B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
General health, weight, basic reflexes, sensory responses, locomotor function, anxiety level, and gross motor function were not different from age-matched controls (Polydoro et al., 2009).
Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy
Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus.
Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal.
Yes
C59Bl/6J
C57BL/6-Tg(tetO-MAPT*A152T)L1Lms/J
Increase in basal synaptic activity and epileptiform spikes. Life span normal.
Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy
Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses.
Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal.
Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy
Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis.
Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months.
Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity.
Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.
Yes
C57BL/6
B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax
On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures.
Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord.
By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization.
Yes
C57BL/6, DBA/2, SW Mixed Background
Tg(Prnp-MAPT*P301L)JNPL3Hlmc
Eye irritiation, possibily due to carrying the Pde6brd1 retinal degeneration mutation
carries Pde6brd1 mutation
Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology.
Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test.
Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region.
Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration.
Yes
C57BL/6 x DBA
mThy1-hAβPP751 Swe Lon
Available through Eliezer Masliah. The CRO PsychoGenics offers research services with this line.
Human ApoE3 protected against the age-dependent neurodegeneration seen in APOE -/- mice.
Unknown.
No
Origin: C57BL/6J; backcrossed with murine APOE-null mice
Widespread neuronal expression of ApoE in the brain. Expression of ApoE3 protected against kainic acid-induced neuronal damage (loss of synaptophysin-positive presynaptic terminals and MAP2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus).
NSE-ApoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and seen primarily in females.
No
Origin: C57BL/6J; backcrossed with murine ApoE-null mice
Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against kainic acid-induced neuronal damage.
Behavioral deficits in the water maze at 12 months in mice expressing mutatnt as well as wild-type PSEN2, including longer escape latencies than wild-type mice, but no difference in swimming speed.
No
C57BL/6× DBA/2
Expression of PSEN2 was higher in mice expressing mutant as well as wild-type PSEN2 compared to age-matched, non-transgenic mice. Alterations in levels of Aβ42, caspase-3 and Cox-2 proteins.
Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus.
Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months.
Yes
C57B6 x DBA2
Alterations in sleep/wake states, thermoregulation, and motor activity.
Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months.
Unknown.
No
C57BL/6
Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition.
Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT.
Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity.
Yes
C57BL6
Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep.
Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology.
Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety.
Yes
C57BL/6J, for at least six generations
Breeding, litter size, and overall health are normal. Reduced body weight in knock-in animals after six months of age in males and nine months in females.
Histologically normal up to 2 years old by hematoxylin-eosin, silver, and thioflavin-S staining.
Learning and spatial memory were unaffected in the water maze test. Neither the escape latency nor escape pathway was different from PSEN1 wild-type mice at 1 and 9 months of age.
No
FVB/N
Tg(Thy1-PSEN1*A246E)2Vln/0
Mice are more sensitive to kainic acid displaying greater KA-induced seizure activity and neuronal damage. LTP induced by a strong stimulus was not altered, but a weak stimulation at synapses between Schaeffer’s collaterals and CA1 pyramidal neurons elicited LTP only in mutant mice.
Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments.
Subtle but significant deficits in long-term spatial memory in the Morris water maze.
Yes
CaM-Cre tg mice were generated in C57BL/6J x CBA hybrid, and then back-crossed several generations to C57BL/6J. The floxed PS1 mouse was generated in C57BL/6J and 129/Sv hybrid.
No abnormal pathology up to 2.5 years. Elevated Aβ2(43); no effect on Aβ40. Altered mitochondrial activity. Disregulation of calcium homeostasis.
No difference from wild-type mice in the “Y” maze (alternation performance or activity) at 12-14 weeks.
No
B6/D2/Swe/SJL mixed background
Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with wild-type mice. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection.
Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months.
Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months.
Yes
C57BL/6
Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz
Decreased survival of newborn neurons in the dentate gyrus at about 4 months. Reduced endoplasmic reticulum Ca2+ and calcium dysregulation. A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of 10 month old animals compared to wild-type mice. Decreased perfusion in the occipital cortex at all ages tested (10-17 months).
Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition.
Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze.
Yes
C57BL/6, DLB/2, crossed to C57BL/6
Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr
More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months. Loss of metabotropic glutamate receptors (mGlu2) in certain brain regions of aged mice as demonstrated by autoradiography.
Originally generated in a B6.D2 background, then crossed into C57BL/6J.
Tg(Prnp-PSEN2*N141I)30Jgr
Ubiquitous expression of mutant transgene. Brain homogenate from 2 week-old mice had PSEN levels 1.8-2.2 fold higher than wild-type mice. Disrupted Ca2+ homeostasis, similar to that of double transgenic PS2APP mice, including a reduction in endoplasmic reticulum Ca2+ content in cultured neurons and a generally decreased response to metabotropic agonists.
Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation.
Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels.
Yes
B6/D2/Swe/SJL mixed background
Selective increase in brain Aβ42(43) in the double transgenics (41% increase at 6 weeks) compared to Tg2576 single transgenic, which had unchanged Aβ40 and Aβ42(43) at this age.
At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus.
Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age.
No morphological abnormalities. When crossed with Cre recombinase driven by Thy1, brain levels of Aβ40 and Aβ42 decrease and C-terminal fragments of APP accumulate.
When crossed with Cre recombinase driven by Thy1, no cognitive deficit in an object recognition task.
No
Origin: 129P2/OlaHsd; backcrossed to C57BL/6
B6;129P-Psen1tm1Vln/J
When crossed with Cre recombinase driven by Thy1, LTP induction is slightly altered.
Hypersensitive to kainate-induced degeneration and death of CA3, CA1 and hilar neurons. Cultured hippocampal neurons have increased vulnerability to death induced by glutamate. Disrupted calcium homeostasis. Increased oxidative stress and mitochondrial dysfunction.
Unknown.
No
C57BL/6
B6.129-Psen1tm1Mpm/J
Mice are viable, fertile, and normal in size. No gross physical or behavioral abnormalities.
Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers.
No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests.
Yes
129S6FVB F1
Reduced body weight at 24-27 months relative to non-Tg littermates and those expressing only tTA.
Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss.
Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test.
Yes
4510 mice are on an FVB background. Neuropsin-tTA mice are on a C57BL/6 background.
No apparent change in anxiety as assessed by the open field test. Reduced Arc induction in the hippocampus after contextual fear conditioning. Subtle differences in basal synaptic transmission with enhanced axonal excitability.
Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau.
Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved.
Homozygous mice are not viable. It should be noted that disruption of an endogenous mouse gene, caused by random insertion of the MAPT transgene, significantly contributes to the neuropathological and neurodegenerative phenotypes observed in rTg4510 mice
Age-associated increase in hippocampal Aβ from 4 to 12 months, but no plaque-like structures by Congo red or thioflavine S. Spongiform degeneration: vacuoles of various size in the neuropil in the brain stem. Microglial cell proliferation. Degeneration of dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus.
Age-associated behavioral impairments including learning and memory difficulties, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythms of spontaneous motor activity and drinking behaviours.
Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes.
Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning.
Yes
Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6
No differences in body temperature, locomotor activity, or Rotarod performance, relative to non-Tg controls.
Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology.
Age-dependent impairment in object recognition memory starting around 6 months of age.
Yes
TAS10 transgene originally injected into C57BL/6 x C3H oocytes, with some backcrossing to C57BL/6. TPM generated on pure C57BL/6 background.
Progressive Supranuclear Palsy, Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy
Progressive tau pathology in the hippocampus, including abnormally phosphorylated and misfolded tau, mislocalized tau, and tangle-like structures. Dystrophic neurites.
Impaired spatial learning and memory in the Morris water maze. Early motor impairments, including abnormal limb clasping, Rotarod deficits and decreased grip strength.
Yes
C57BL/6 (75%) and 129/Ola (25%).
Muscle fibers in the quadriceps and latissimus muscles appeared to be degenerative/regenerative. Progressive spine curvature.
Frontotemporal Dementia, Other Tauopathy, Alzheimer's Disease
Extensive pretangle pathology throughout the brain (e.g. phospho- tau) but no mature neurofibrillary tangles and only mild oligomeric tau, restricted to the CA1 region of the hippocampus. Dystrophic neurites and axonal pathology (spheroids). No overt neuronal loss.
Motor deficits develop with age, including decreased grip strength and impaired Rotarod performance. Cognitive deficits, indicative of impaired spatial learning and memory, as assessed by the Barnes maze.
Yes
C57BL/6J
B6.Cg-Tg(Thy-MAPT*)2652Gds
Homozygous mice have reduced body weight, reduced fertility, and premature death. Some homozygous mice also exhibit seizure activity.
Frontotemporal Dementia, Alzheimer's Disease, Other Tauopathy
Aggregated tau in neurons of the entorhinal cortex, hippocampus, and cerebral cortex at advanced ages. Intraneuronal accumulation of tau oligomers in the hippocampus. Neuronal loss in the entorhinal cortex and hippocampus. Gliosis. Some hippocampal areas affected by age-related synaptic dysfunction and reduced synaptic density.
Impaired spatial reference memory as measured by the Morris water maze by 6 months of age.
Yes
B6C3F1 embryos, backcrossed to C57BL/6
Human tau transcripts containing exon 10 are over-represented in the adult mouse brain, leading to elevated levels of 4R tau relative to 3R tau.
Available through Hiroshi Mori and Takami Tomiyama
No significant cell loss or astrogliosis in the brain. Age-dependent reduction in synaptic proteins (e.g. synaptophysin, PSD95) by 1.3 to 3 months of age. Hyperphosphorylated tau oligomers and aggregates.
Learning and memory deficits by 1.3 to 3 months of age, as assessed by the Y-maze and passive avoidance tests. No significant motor impairment.
Age-dependent deterioration of sensorimotor functions, including coordination deficits on the Rotarod and a decrease in muscle strength. No deficits in learning or memory.
No
Mixed background (BALB/c x C57B1/B6 x B6D2F1)
Humanized splicing pattern of murine tau, leading to the production of 3R tau rather than 4R tau. No anxiety phenotype.
Abundant pre-tangle pathology, but only rare mature tangles, and only at advanced ages. Tau pathology included mislocalization of tau to the somatodendritic compartment, aggregation, and hyperphosphorylation.
Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF.
Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months.
Yes
FVB/N
Thy1-hTau.P301L
Premature death around 8-12 months, preceded by weight loss, hyperkyphosis, reduced activity, and upper airway dysfunction.
The CRO reMYND offers research services with this line.
Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis.
Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months.
Yes
(C57BL/6 x C3H)F1
B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J
Clasping and limb retraction when lifted by the tail at three months, followed by limb weakness and brain atrophy. Homozygous females do not mate.
Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss.
Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology.
Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and ROS compared to wild-type. No differences in APP expression, APP cleavage or Aβ accumulation compared to PS2APP. Levels of ptau422 increased in an age-dependent manner, but levels of ptau231 did not.
Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments.
Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.
Yes
B6SJL/F1; backcrossed to C57BL/6J
No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests). Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality.
Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss.
Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance.
Yes
C57BL/6
Missorting of tau into the somato-dendritic compartment. Calcium dysregulation at synaptic boutons. Deficits in synaptic plasticity, including LTP and LTD.
SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure.
Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze.
Yes
B6SJL/F1
The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels. In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response.
Intraneuronal accumulation of Aβ peptides in the hippocampus by 3 months and in cerebellar nuclei by 6 months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits.
Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 or 6 months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at 3 and 6 months as indicated by the balance-beam test, but impairment at 12 months.
APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885.
APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885.
APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107.
Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles or neuronal loss.
Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months.
Yes
B6;SJL Mixed Background
B6;SJL-Tg(APPSWE)2576Kha
Between 7 -12 weeks males become aggressive and begin to fight. Premature mortality: mortality of >20% anticipated, particularly in males.
Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis.
Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming.
Yes
C57BL/6, DBA/2, SJL, SW Mixed Background
Tg(APPSWE)2576Kha; Tg(Prnp-MAPT*P301L)JNPL3Hlmc
Progressive hindlimb weakness. Hunched posture. Eye irritations. Some mice have the Pde6brd1 retinal degeneration mutation which can cause light sensitivity and/or blindness and may affect behavioral testing.
Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis.
Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning.
Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females.
Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months.
Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months).
Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus.
Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months.
Yes
C57BL/6J
Tg-ArcSwe have reduced body weight compared with nontransgenic littermates.
Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months .
Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests.
Yes
Hybrid C3H/He-C57BL/6
Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition.
Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto
Widespread cerebral amyloid angiopathy (CAA) starting around 7 months. Deposition of the Danish amyloid subunit (ADan) in brain parenchyma and vessels, along with amyloid-associated gliosis and inflammation, intracellular and extracellular deposition of oligomeric ADan, and tau-positive deposits in neuropil, but no neurofibrillary tangles.
Age-dependent abnormal grooming behavior. Around one year mice develop an arched back and walk with a wide-based gait and short steps. Feet clasping upon suspension of the mice by their tails.
Increased activation of microglia and astrocytes compared to mice expressing mutant APP alone.
Abnormalities in spatial learning and memory at 3-4 months of age, whereas deficits occur later in mice expressing mutant APP alone and are less severe.
Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type
Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months.
Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination.
A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis.
Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity.
Yes
C57BL6/CBA; backcrossed to C57BL6
Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission.
Brain is grossly normal. Age-dependent cholinergic neurodegeneration and reduced NGF in the basal forebrain. Age-related elevation of APP and Aβ in the hippocampus but no β-amyloid pathology.
Early developmental delay. Deficits in behavioral and cognitive tasks including spatial learning and memory deficits as assessed by the Morris water maze and the radial arm maze. Developmental delay in sensorimotor milestones. Locomotor hyperactivity. Lack of behavioral inhibition. Stereotypic behavior.
No
DBA/2J
B6EiC3Sn a/A-Ts(1716)65Dn/J
Females are smaller, and produce fewer, smaller litters. Males are effectively sterile with hypospermia.