Updated 30 December 2008

General Information

Transgene/Mutation: Mouse pronuclei (B6C3H) were injected with a transgenic construct containing a cDNA encoding a chimeric amyloid beta (A4) precursor protein (APP695) regulated by the mouse prion promoter. The chimeric APP695 molecule was created by replacing sequences encoding the Abeta domain of the murine sequence with the cognate sequences of the human gene and mutations K595N and M596L (APP695 isoform numbering).

Breeding: Origin: (C57BL/6J x C3H/HeJ)F2

Strain: C3B6-Tg(APP695)3Dbo/J

Phenotype

Neuropathological Analysis:

Development of amyloid deposits observed in cortex and hippocampus of 18-20 months of age. Ratio of amyloid-β peptide 40:42 is 3:1

Behavioral Phenotype:

Memory deficits

Availability

Terms and Conditions: This strain is not available to companies or for profit entities, it is available to research institutions for non-commercial research.

Contact: The Jackson Lab, stock 003375

References

Primary:

Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, Prada CM, Kim G, Seekins S, Yager D, Slunt HH, Wang R, Seeger M, Levey AI, Gandy SE, Copeland NG, Jenkins NA, Price DL, Younkin SG, Sisodia SS. Related Articles, Links Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron. 1996 Nov;17(5):1005-13. Abstract

Associated:

Cai D; Zhong M; Wang R; Netzer WJ; Shields D; Zheng H; Sisodia SS; Foster DA; Gorelick FS; Xu H; Greengard P. 2006. Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons. Proc Natl Acad Sci U S A 103(6):1936-40. Abstract

Simard AR; Soulet D; Gowing G; Julien JP; Rivest S. 2006. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49(4):489-502. Abstract

Stokin GB; Lillo C; Falzone TL; Brusch RG; Rockenstein E; Mount SL; Raman R; Davies P; Masliah E; Williams DS; Goldstein LS. 2005. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 307(5713):1282-8. Abstract

Jankowsky JL; Melnikova T; Fadale DJ; Xu GM; Slunt HH; Gonzales V; Younkin LH; Younkin SG; Borchelt DR; Savonenko AV. 2005. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. J Neurosci 25(21):5217-24. Abstract

Kalesnykas G; Roschier U; Puolivali J; Wang J; Miettinen R. 2005. The effect of aging on the subcellular distribution of estrogen receptor-alpha in the cholinergic neurons of transgenic and wild-type mice. Eur J Neurosci 21(5):1437-42. Abstract

Perez SE; Lazarov O; Koprich JB; Chen EY; Rodriguez-Menendez V; Lipton JW; Sisodia SS; Mufson EJ. 2005. Nigrostriatal dysfunction in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 transgenic mice. J Neurosci 25(44):10220-9. Abstract

Savonenko A; Xu GM; Melnikova T; Morton JL; Gonzales V; Wong MP; Price DL; Tang F; Markowska AL; Borchelt DR. 2005. Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis 18(3):602-17. Abstract

Jankowsky JL; Fadale DJ; Anderson J; Xu GM; Gonzales V; Jenkins NA; Copeland NG; Lee MK; Younkin LH; Wagner SL; Younkin SG; Borchelt DR. 2004. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159-70. Abstract

Jankowsky JL; Slunt HH; Gonzales V; Jenkins NA; Copeland NG; Borchelt DR. 2004. APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiol Aging 25(7):885-92. Abstract

Wang J; Tanila H; Puolivali J; Kadish I; van Groen T. 2003. Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Neurobiol Dis 14(3):318-27. Abstract

van Groen T; Liu L; Ikonen S; Kadish I. 2003. Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions. Neuroscience 119(4):1185-97. Abstract

Liu L; Tapiola T; Herukka SK; Heikkila M; Tanila H. 2003. Abeta levels in serum, CSF and brain, and cognitive deficits in APP + PS1 transgenic mice. Neuroreport 14(1):163-6. Abstract

Savonenko AV; Xu GM; Price DL; Borchelt DR; Markowska AL. 2003. Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE. Neurobiol Dis 12(3):194-211. Abstract

Xiang Z; Ho L; Valdellon J; Borchelt D; Kelley K; Spielman L; Aisen PS; Pasinetti GM. 2002. Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of Alzheimer's disease neuropathology. Neurobiol Aging 23(3):327-34. Abstract

Wang J; Ikonen S; Gurevicius K; van Groen T; Tanila H. 2002. Alteration of cortical EEG in mice carrying mutated human APP transgene. Brain Res 943(2):181-90. Abstract

Lesuisse C; Xu G; Anderson J; Wong M; Jankowsky J; Holtz G; Gonzalez V; Wong PC; Price DL; Tang F; Wagner S; Borchelt DR. 2001. Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice. Hum Mol Genet 10(22):2525-37. Abstract

Borchelt DR; Ratovitski T; van Lare J; Lee MK; Gonzales V; Jenkins NA; Copeland NG; Price DL; Sisodia SS. 1997. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19(4):939-45. Abstract

Borchelt DR; Davis J; Fischer M; Lee MK; Slunt HH; Ratovitsky T; Regard J; Copeland NG; Jenkins NA; Sisodia SS; Price DL. 1996. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal 13(6):159-63. Abstract