Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: AKR/J, suspected outbreeding to unknown line
Availability: Envigo (formerly Harlan): SAMP8-TaHsd
The Senescence Accelerated Mouse-Prone 8 (SAMP8) is a naturally occuring mouse line that displays a phenotype of accelerated aging. While maintaining an inbred AKR/J line in the early 1970's, researchers at Kyoto University became aware that some of the progeny exhibited a moderate to severe degree of activity loss, hair loss, lordokyphosis and early death. Several lines of senescence accelrated animals were established (SAM-P/1, SAM-P/2, SAM-P/3, and SAM-P/4) along with several lines of senescence resistant strains (with normal aging). The SAMP8 line is derived from the SAM-P/2 line.
The SAMP mice, including SAMP8, have been widely used in aging research to study phenotypes such as immune dysfunction, osteoporosis, and brain atrophy. The mice have apparently normal early development with no evidence of growth retardation. Despite intense characterization of SAMP strains, the genes responsible for the accelerated senescence and pathologic changes remain largely unknown.
Age-associated increase in hippocampal Aβ from four to twelve 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 (Yagi et al., 1989). Microglial cell proliferation (Amano et al., 1995). Degeneration of dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus (Karasawa et al., 1997).
Age-associated behavioral impairments including learning and memory difficulties (Miyamoto et al., 1986), emotional disorders, such as reduced anxiety-like behavior and depressive behavior (Miyamoto et al., 1992) and altered circadian rhythms of spontaneous motor activity and water consumption (Miyamoto, 1997).
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- Canudas AM, Gutierrez-Cuesta J, Rodríguez MI, Acuña-Castroviejo D, Sureda FX, Camins A, Pallàs M. Hyperphosphorylation of microtubule-associated protein tau in senescence-accelerated mouse (SAM). Mech Ageing Dev. 2005 Dec;126(12):1300-4. PubMed.
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- Poon HF, Castegna A, Farr SA, Thongboonkerd V, Lynn BC, Banks WA, Morley JE, Klein JB, Butterfield DA. Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain. Neuroscience. 2004;126(4):915-26. PubMed.
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- Farr SA, Banks WA, Uezu K, Sano A, Gaskin FS, Morley JE. Antibody to beta-amyloid protein increases acetylcholine in the hippocampus of 12 month SAMP8 male mice. Life Sci. 2003 Jun 20;73(5):555-62. PubMed.
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- Kumar VB, Farr SA, Flood JF, Kamlesh V, Franko M, Banks WA, Morley JE. Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice. Peptides. 2000 Dec;21(12):1769-75. PubMed.
- Ohta A, Hirano T, Yagi H, Tanaka S, Hosokawa M, Takeda T. Behavioral characteristics of the SAM-P/8 strain in Sidman active avoidance task. Brain Res. 1989 Sep 25;498(1):195-8. PubMed.
- Flood JF, Morley JE. Early onset of age-related impairment of aversive and appetitive learning in the SAM-P/8 mouse. J Gerontol. 1992 Mar;47(2):B52-9. PubMed.
- Cheng XR, Zhou WX, Zhang YX. The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer's disease animal model. Ageing Res Rev. 2014 Jan;13:13-37. Epub 2013 Nov 21 PubMed.