General Information

Transgene:     PS1 cDNA, (VRSQ-)

Mutation:         M146V

Targeted region (if applicable):     n/a

Promoter:         Rat PDGF b-chain (1.4 kb Xba fragment),

Coding region:     1.4 kb PS1 coding region from ATG start to TGA stop site

Intron:         3 kb PS1 intron 5 inserted at endogenous locus in cDNA Poly A tail from SV40

Mouse strain:     Swiss webster (taconic) x B6D2F1 (taconic)

Phenotype

Null mutant phenotype:     n/a

Lethality/viability/fecundity:     normal for all parameters. Above average fecundity.

Homozygous/heterozygous viability:     both are viable

Relative Protein expression level to endogenous:
Beta Amyloid:     n/a
Presenilin:     2-3 folds (by quantitative western)
Tau:     n/a

Neuropathological Analysis:

No abnormal pathology up to 2.5 years. Elevated Aβ-42 (Duff, 1996); altered mitochondria activity (Bengley, 1999), disregulation of calcium homoeostasis (Bengley, 1999; Barrow, 2000).

Behavioral:

No abnormal behavior in Morris water maze (Duff, 1996); no abnormal behavior seen in spontaneous alternation test and other test (Holcomb, 1998 and 1999). Electrophysiological assessment: altered AHP in mutants (Barrow, 2000).

Crosses to create multigenic mouse:

Crossed to APP Tg2576 to create the PS/APP line (Holcomb, 1998 and 1999; Wong, 1999; McGowan, 1999; Takeuchi, 2000, Refolo, 2000; Helpern, 2004; Lee, 2004).

Availability

Licensing/academic distribution contact information:

Wendy Davies,
University of South Florida  
WDAVIS@RESEARCH.USF.EDU

Patents:   

Reference

Primary:

Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-Tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon MN, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature. 1996 Oct 24 ; 383(6602):710-3. Abstract.

Associated:

Barrow PA, Empson RM, Gladwell SJ, Anderson CM, Killick R, Yu X, Jefferys JG, Duff K Functional Phenotype in Transgenic Mice Expressing Mutant Human Presenilin-1. Neurobiol Dis 2000 7, 119-126. Abstract.

Begley JG, Duan W, Chan S, Duff K, Mattson MP. Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice. J Neurochem. 1999 Mar ; 72(3):1030-9. Abstract.

Related:

Lee SP, Falangola MF, Nixon RA, Duff K, Helpern JA Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents. Magn Reson Med. 2004 Sep;52(3):538-44. Abstract

Helpern JA, Lee SP, Falangola MF, Dyakin VV, Bogart A, Ardekani B, Duff K, Branch C, Wisniewski T, de Leon MJ, Wolf O, O'Shea J, Nixon RA MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease. Magn Reson Med. 2004 Apr;51(4):794-8. Abstract

L. Refolo, M. Pappolla, B. Malester, J. LaFrancois, R. Wang, G. Tint, K. Sambamurti, T. Bryant-Thomas and K. Duff. Hypercholesterolemia accelerates amyloid pathology in a transgenic mouse model for Alzheimer?s disease amyloidosis. Neurobiol Dis. 2000 Aug;7(4):321-31. Abstract.

Takeuchi A, Irizarry MC, Duff K, Saido TC, Hsiao Ashe K, Hasegawa M, Mann DM, Hyman BT, Iwatsubo T. Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss. Am J Pathol. 2000 Jul ; 157(1):331-9. Abstract.

McGowan E, Sanders S, Iwatsubo T, Takeuchi A, Saido T, Zehr C, Yu X, Uljon S, Wang R, Mann D, Dickson D, Duff K. Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol Dis. 1999 Aug ; 6(4):231-44. Abstract.

Holcomb LA, Gordon MN, Jantzen P, Hsiao K, Duff K, Morgan D. Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav Genet. 1999 May ; 29(3):177-85. Abstract.

Wong TP, Debeir T, Duff K, Cuello AC. Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. J Neurosci. 1999 Apr 1 ; 19(7):2706-16. Abstract.

Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, Wright K, Saad I, Mueller R, Morgan D, Sanders S, Zehr C, O'Campo K, Hardy J, Prada CM, Eckman C, Younkin S, Hsiao K, Duff K. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med. 1998 Jan 1 ; 4(1):97-100. Abstract.