General Information

Transgene:     PS1 cDNA, (VRSQ-)

Mutation:       Δ9, wt

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:

Histological:     no abnormal pathology up to 2.5 yrs of age

Immunchemical:     no abnormal pathology up to 2.5 yrs of age

Structural:     none

Behavioral:

Morris Water Maze: Abnormal behavior not seen

Other: no behavioral abnormalities seen (spontaneous alternation test and others, see refs 4, 7)

Electrophysiological assessment: altered AHP in mutants (see ref 3)

Other: elevated Ab42 (ref 1), altered mitocondrial activity (see ref 2), disregulation of calcium homeostasis (see refs 2 and 3)

Crosses to create multigenic mouse:     crosses to APPTg2576 to create the PS/APP line, see refs 4-9

Availability

Licensing/academic distribution contact information:

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

Patents:   

Reference

Primary:

1. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M.N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J. and Younkin, S. (1996) Increased amyloid-Beta 42(43) in brains of mice expressing mutant presenilin 1. Nature 383 710-713. Abstract.

2. Bengley J, Duan W, Chan S, Duff K and Mattson M. (1999) Altered calcium homeostasis and mitocondrial dysfunction in cortical synaptic compartments of PS1 mutant mice. J. Neurochem, 72 (3) 1030-1039. Abstract.

3. 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.

Associated:

4. Holcomb L, Gordon M, 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 C, Eckman C, Younkin S, Hsiao K, Duff K. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nature. Med, Vol. 4 (No 1); p.97. Abstract.

5. T-P Wong, T. Debeir, K. Duff, and A.C Cuello. (1999) Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1, and amyloid precursor protein transgenes J. Neuroscience, 19 (7) 2706-2716. Abstract.

6. McGowan E, Sanders S, Iwatsubo T, Takeuchi A, Saido T, Zehr C, Yu X, Uljon, S.E., Wang R, Mann D, Dickson D, Duff K. (1999) Amyloid phenotype characterization of transgenic mice over-expressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol. Dis 6, 231-244. Abstract.

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

8. A. Takeuchi, E. M. Irizarry, K. Duff, T. Saido, K. Hsiao Ashe, D. Mann , B Hyman and T. Iwatsubo. 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 los  (Am J Pathol 2000, vol 157 p.331-339). Abstract.

9. 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.