Posted 1 April 2005

General Information

Transgene: Human PS1A246E transgene under the control of human Thy-1 promoter was generated by ligating a 1.4 kb KpnI-BamHI fragment containing PS1A246E cDNA sequence with a KpnI-BglII-cleaved pHZ024 vector, which contains the human Thy-1 promoter.

Mutation: Human PS1(A246E)

Promoter: Thy-1

Mouse Strain: B6SJL/F1

Phenotype

Neuropathological Analysis:

Human PS1 transgenic mice were mated with heterozygous PS1 knockout mice (mPS1^+/-) (Wong, 1997). Transgenic mouse lines expressing human PS1 with the A246E FAD mutation can rescue the PS1 knockout mouse from embryonic lethality, indicating that the mutation does not lead to loss of PS1 function during development. Furthermore, a 50% reduction of PS1 activity in PS1(+/-) mice does not lead to Aβ1-42/43 increase, whereas expression of human mutant PS1 on murine PS1 null background is sufficient to elevate Aβ1-42/43, supporting a gain-of-function activity as the result of the PS1 mutation.

Behavioral:

No overt abnormalities were observed in the mutant human PS1 transgenic mice.

Availability

Hui Zheng
Huffington Center on Aging
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX 77030
Phone: (713) 798-1568
Fax: (713) 798-1610
Email: huiz@bcm.tmc.edu

Patents:

Patent No.: 6,452,065 B2
Title: Transgenic mouse expressing non-native wild-type and familial Alzheimer's disease mutant presenilin 1 protein on native presenilin 1 null background
Assignee/Inventors: H. Zheng, P. Jiang, S. Qian, L. Van der Ploeg, P. C. Wong, S. Sisodia
Filing Date: 5/14/98
Issue Date: 9/17/02

Reference

Primary:

Su Qian, Ping Jiang, Xiao-Ming Guan, Gurparkash Singh, Myrna E. Trumbauer, Hong Yu, Howard Y. Chen, Lex H. T. Van der Ploeg and Hui Zheng. Mutant Human Presenilin 1 Protects presenilin 1 Null Mouse against Embryonic Lethality and Elevates Ab1-42/43 Expression. Neuron 20: 611-617, 1998. Abstract

Associated:

Wilson CA, Murphy DD, Giasson BI, Zhang B, Trojanowski JQ, Lee VM. Degradative organelles containing mislocalized a- and β-synuclein proliferate in presenilin-1 null neurons. J Cell Biol. 165(3): 335-46, 2004. Abstract

P.C. Wong, H. Zheng, H. Chen, M.W. Becher, D.J.S. Sirinathsinghji, M.E. Trumbauer, H.Y. Chen, D.L. Price, L.H.T. Van der Ploeg and S.S. Sisodia. Presenilin is required for Notch1 and Dll1 expression in the paraxial mesoderm. Nature 387:288-292, 1997. Abstract