General Information

Updated 30 October 2005

Transgene: Mouse pronuclei (B6D2F1) were injected with a transgenic construct (blunt-ended XhoI) containing cDNA encoding hAPP751 with Swedish mutation regulated by the murine Thy-1.2 promoter.

Promoter: murine Thy-1.2 gene

Mouse Strain: Origin: C57B/6

Phenotype

Neuropathological Analysis:

Mice have a 7 fold overexpression of APP and first show Aβ deposits at 6 months of age. Deposits increase with age in size and number and eventually occupy a substantial area of the neocortex and hippocampus in 24 month old mice. Associated with the amyloid are inflammatory reactions, neuritic and synaptic degeneration as well as tau hyperphosphorylation. The plaque cores are substantially more soluble than those in the AD brain. The mice show more congophilic plaque, high levels of Aβ in cerebrospinal fluid, and regional localization of cerebral amyloid angiopathy (CAA). Cerebral amyloidosis is not sufficient to account for global synapse loss in AD (Boncristiano, 2005).

Behavior and age of phenotype:

• Passive avoidance memory, 25 months (progressive) (Kelly et al., 2003)
• WM spatial memory retention acquisition, 3, 6, 18, 25 months (progressive) (Kelly et al., 2003)
• Hyperactivity, 6-8 weeks, 3, 6 months (Van Dam et al., 2003)
• Rotorod performance, 3, 6 months (Van Dam et al., 2003)
• Open field, 3, 6 months (Van Dam et al., 2003)
• Vascular amyloidosis, spontaneous microhemorrhages, 12 months (Winkler et al., 2001)

Availability

Contact:
Matthias Staufenbiel
Novartis Pharma, Inc.,
S-386.809, CH-4002 Basel, Switzerland
Email: Matthias Staufenbiel

Patents: None

References

Primary:

Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA, Waridel C, Calhoun ME, Jucker M, Probst A, Staufenbiel M, Sommer B. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci U S A 1997 Nov 25;94(24):13287-92. Abstract.

Associated:

Boncristiano S, Calhoun ME, Howard V, Bondolfi L, Kaeser SA, Wiederhold KH, Staufenbiel M, Jucker M. Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice. Neurobiol Aging. 2005 May;26(5):607-13. Abstract

Lalonde R, Dumont M, Staufenbiel M, Strazielle C. Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen. Behav Brain Res. 2005 Feb 10;157(1):91-8. Abstract

Sykova E, Vorisek I, Antonova T, Mazel T, Meyer-Luehmann M, Jucker M, Hajek M, Ort M, Bures J. Changes in extracellular space size and geometry in APP23 transgenic mice: a model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):479-84. Epub 2005 Jan 3. Erratum in: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2671. Abstract

Van Dam D, Marescau B, Engelborghs S, Cremers T, Mulder J, Staufenbiel M, De Deyn PP. Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of two APP overexpression mouse models. Neurochem Int. 46(5): 409-22, 2005. Abstract

Van Dam D, Vloeberghs E, Abramowski D, Staufenbiel M, De Deyn PP. APP23 Mice as a Model of Alzheimer's Disease: An Example of a Transgenic Approach to Modeling a CNS Disorder. CNS Spectr. 10(3):2 07-22, 2005. Abstract

Boncristiano S, Calhoun ME, Howard V, Bondolfi L, Kaeser Sa, Wiederhold KH, Staufenbiel M, Jucker M. Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP 23 transgenic mice. Neurobiol Aging 26(5):607-613, 2005. Abstract

Van Dam D, Abramowski D, Staufenbiel M, De Deyn PP. Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model. Psychopharmacology on line Jan 15, 2005. Abstract

Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem. 2005 Feb 11;280(6):4079-88. Abstract

Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS. The LXR ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem. 2004 Nov 22. Abstract

Dumont M, Strazielle C, Staufenbiel M, Lalonde R. Spatial learning and exploration of environmental stimuli in 24-month-old female APP23 transgenic mice with the Swedish mutation. Brain Res. 2004 Oct 22;1024(1-2):113-21. Abstract

Burbach GJ, Dehn D, Del Turco D, Staufenbiel M, Deller T. Laser microdissection reveals regional and cellular differences in GFAP mRNA upregulation following brain injury, axonal denervation, and amyloid plaque deposition. Glia. 2004 Oct;48(1):76-84. Abstract

Mueggler T, Meyer-Luehmann M, Rausch M, Staufenbiel M, Jucker M, Rudin M. Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis.Eur J Neurosci. 2004 Aug;20(3):811-7. Abstract

Vloeberghs E, Van Dam D, Engelborghs S, Nagels G, Staufenbiel M, De Deyn PP. Altered circadian locomotor activity in APP23 mice: a model for BPSD disturbances. Eur J Neurosci. 20(10): 2757-66, 2004. Abstract.

Okamura N, Suemoto T, Shimadzu H, Suzuki M, Shiomitsu T, Akatsu H, Yamamoto T, Staufenbiel M, Yanai K, Arai H, Sasaki H, Kudo Y, Sawada T. Styrylbenzoxazole derivatives for in vivo imaging of amyloid plaques in the brain. J Neurosci. 2004 Mar 10;24(10):2535-41. Abstract

Burbach GJ, Hellweg R, Haas CA, Del Turco D, Deicke U, Abramowski D, Jucker M, Staufenbiel M, Deller T. Induction of brain-derived neurotrophic factor in plaque-associated glial cells of aged APP23 transgenic mice. J Neurosci. 24(10):2421-30, 2004. Abstract

Okamura N, Suemoto T, Shiomitsu T, Suzuki M, Shimadzu H, Akatsu H, Yamamoto T, Arai H, Sasaki H, Yanai K, Staufenbiel M, Kudo Y, Sawada T. A novel imaging probe for in vivo detection of neuritic and diffuse amyloid plaques in the brain. J Mol Neurosci. 2004;24(2):247-55. Abstract

Krucker T, Schuler A, Meyer EP, Staufenbiel M, Beckmann N. Magnetic resonance angiography and vascular corrosion casting as tools in biomedical research: application to transgenic mice modeling Alzheimer's disease. Neurol Res. 2004 Jul;26(5):507-16. Abstract

Schwab C, Hosokawa M, McGeer PL. Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp Neurol. 2004 Jul;188(1):52-64. Abstract

Fassbender K, Walter S, Kuhl S, Landmann R, Ishii K, Bertsch T, Stalder AK, Muehlhauser F, Liu Y, Ulmer AJ, Rivest S, Lentschat A, Gulbins E, Jucker M, Staufenbiel M, Brechtel K, Walter J, Multhaup G, Penke B, Adachi Y, Hartmann T, Beyreuther K. The LPS receptor (CD14) links innate immunity with Alzheimer's disease. FASEB J. 2004 Jan;18(1):203-5. Abstract

Diez M, Danner S, Frey P, Sommer B, Staufenbiel M, Wiederhold KH, Hokfelt T. Neuropeptide alterations in the hippocampal formation and cortex of transgenic mice overexpressing beta-amyloid precursor protein (APP) with the Swedish double mutation (APP23). Neurobiol Dis. 2003 Dec;14(3):579-94. Abstract

Gartner U, Bruckner MK, Krug S, Schmetsdorf S, Staufenbiel M, Arendt T. Amyloid deposition in APP23 mice is associated with the expression of cyclins in astrocytes but not in neurons. Acta Neuropathol (Berl). 2003 Dec;106(6):535-44. Abstract

Bayer TA, Schafer S, Simons A, Kemmling A, Kamer T, Tepest R, Eckert A, Schussel K, Eikenberg O, Sturchler-Pierrat C, Abramowski D, Staufenbiel M, Multhaup G. Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14187-92. Abstract

Beckmann N, Schuler A, Mueggler T, Meyer EP, Wiederhold KH, Staufenbiel M, Krucker T. Age-dependent cerebrovascular abnormalities and blood flow disturbances in APP23 mice modeling Alzheimer's disease. J Neurosci. 2003 Sep 17;23(24):8453-9. Abstract

Mueggler T, Baumann D, Rausch M, Staufenbiel M, Rudin M. Age-dependent impairment of somatosensory response in the amyloid precursor protein 23 transgenic mouse model of Alzheimer's disease. J Neurosci. 2003 Sep 10;23(23):8231-6. Abstract

Strazielle C, Sturchler-Pierrat C, Staufenbiel M, Lalonde R. Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation. Neuroscience. 2003;118(4):1151-63. Abstract

Kelly PH, Bondolfi L, Hunziker D, Schlecht HP, Carver K, Maguire E, Abramowski D, Wiederhold KH, Sturchler-Pierrat C, Jucker M, Bergmann R, Staufenbiel M, Sommer B. Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol Aging 2003 Mar-Apr;24(2):365-78. Abstract

Meyer-Luehmann M, Stalder M, Herzig MC, Kaeser SA, Kohler E, Pfeifer M, Boncristiano S, Mathews PM, Mercken M, Abramowski D, Staufenbiel M, Jucker M. Extracellular amyloid formation and associated pathology in neural grafts. Nat Neurosci. 2003 Apr;6(4):370-7. Abstract

Van Dam D, D'Hooge R, Staufenbiel M, Van Ginneken C, Van Meir F, De Deyn PP. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci. 2003 Jan;17(2):388-96. Abstract

Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, Mathews PM, Jucker M. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science. 2002 Nov 15;298(5597):1379. Abstract

Lalonde R, Dumont M, Staufenbiel M, Sturchler-Pierrat C, Strazielle C. Spatial learning, exploration, anxiety, and motor coordination in female APP23 transgenic mice with the Swedish mutation. Brain Res. 2002 Nov 22; 956(1): 36-44. Abstract

Buchner M, Huber R, Sturchler-Pierrat C, Staufenbiel M, Riepe MW. Impaired hypoxic tolerance and altered protein binding of NADH in presymptomatic APP23 transgenic mice. Neuroscience. 2002; 114(2): 285-9. Abstract

Mueggler T, Sturchler-Pierrat C, Baumann D, Rausch M, Staufenbiel M, Rudin M. Compromised hemodynamic response in amyloid precursor protein transgenic mice. J Neurosci. 2002 Aug 15; 22(16): 7218-24. Abstract

Winkler DT, Biedermann L, Tolnay M, Allegrini PR, Staufenbiel M, Wiessner C, Jucker M. Thrombolysis induces cerebral hemorrhage in a mouse model of cerebral amyloid angiopathy. Ann Neurol. 2002 Jun; 51(6): 790-3. Abstract

Lutjohann D, Brzezinka A, Barth E, Abramowski D, Staufenbiel M, von Bergmann K, Beyreuther K, Multhaup G, Bayer TA. Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J Lipid Res. 2002 Jul; 43(7):1078-85. Abstract

Boncristiano S, Calhoun ME, Kelly PH, Pfeifer M, Bondolfi L, Stalder M, Phinney AL, Abramowski D, Sturchler-Pierrat C, Enz A, Sommer B, Staufenbiel M, Jucker M. Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. J Neurosci. 2002 Apr 15; 22(8): 3234-43. Abstract

Bondolfi L, Calhoun M, Ermini F, Kuhn HG, Wiederhold KH, Walker L, Staufenbiel M, Jucker M. Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J Neurosci. 2002 Jan 15; 22(2): 515-22. Abstract

Kuo YM, Beach TG, Sue LI, Scott S, Layne KJ, Kokjohn TA, Kalback WM, Luehrs DC, Vishnivetskaya TA, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Weller RO, Roher AE. The evolution of Abeta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease. Mol Med. 2001 Sep;7(9):609-18. Abstract

Luth HJ, Holzer M, Gartner U, Staufenbiel M, Arendt T. Expression of endothelial and inducible NOS-isoforms is increased in Alzheimer's disease, in APP23 transgenic mice and after experimental brain lesion in rat: evidence for an induction by amyloid pathology. Brain Res. 2001 Sep 14; 913(1): 57-67. Abstract

Stalder M, Deller T, Staufenbiel M, Jucker M. 3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid. Neurobiol Aging. 2001 May-Jun; 22(3): 427-34. Abstract

Kuo YM, Kokjohn TA, Beach TG, Sue LI, Brune D, Lopez JC, Kalback WM, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Roher AE. Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and alzheimer's disease brains. J Biol Chem 2001 Apr 20;276(16):12991-8. Abstract.

Winkler DT, Bondolfi L, Herzig MC, Jann L, Calhoun ME, Wiederhold KH, Tolnay M, Staufenbiel M, Jucker M. Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy. J Neurosci. 2001 Mar 1;21(5):1619-27. Abstract

Bornemann KD, Wiederhold KH, Pauli C, Ermini F, Stalder M, Schnell L, Sommer B, Jucker M, Staufenbiel M. Aβ-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am J Pathol. 2001 Jan; 158(1): 63-73. Abstract.

Phinney AL, Deller T, Stalder M, Calhoun ME, Frotscher M, Sommer B, Staufenbiel M, Jucker M. Cerebral amyloid induces aberrant axonal sprouting and ectopic terminal formation in amyloid precursor protein transgenic mice. J Neurosci. 1999 Oct 1;19(19):8552-9. Abstract

Stalder M, Phinney A, Probst A, Sommer B, Staufenbiel M, Jucker M. Association of microglia with amyloid plaques in brains of APP23 transgenic mice. Am J Pathol. 1999 Jun; 154(6): 1673-84. Abstract

Sturchler-Pierrat C, Staufenbiel M. Pathogenic mechanisms of Alzheimer's disease analyzed in the APP23 transgenic mouse model. Ann N Y Acad Sci 2000;920:134-9. Abstract.

Calhoun ME, Burgermeister P, Phinney AL, Stalder M, Tolnay M, Wiederhold KH, Abramowski D, Sturchler-Pierrat C, Sommer B, Staufenbiel M, Jucker M. Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc Natl Acad Sci U S A 1999 Nov 23;96(24):14088-93. Abstract.

Calhoun ME, Wiederhold KH, Abramowski D, Phinney AL, Probst A, Sturchler-Pierrat C, Staufenbiel M, Sommer B, Jucker M. Neuron loss in APP transgenic mice. Nature. 1998 Oct 22;395(6704):755-6. Abstract