General Information

Transgene:  PS2 cDNA reverse transcribed from normal aged human brain

Mutation:    N141I missense mutation

Promoter:  chicken b-actin promoter

Coding region: EcoRI-BglII fragment subcloned into pCAGGS, joined to the cytomegalovirus immediate early enhancer sequence, the chicken  b-actin promoter, and the rabbit b-globin polyadenylation signal.

Mouse Strain:  C57BL/6 (B6)J or DBF1 fremales and B6N males

Phenotype

Neuropathological analysis:

Steady-state level of  human wild-type and mutant PS2 mRNA was five (mutant) to fifteen (wildtype) higher than that of the endogenous mouse PS2 mRNA.

Ab42 levels appeared to be increase steadily in the mutant PS2 transgenic mouse brains from 2 to 8 months of age, whereas there was only a small increase in wild-type transgenic mice between the age of 5 and 8 months. Similar age-dependent increase in the Ab42 levels as seen in the mutant Tg is also observed in nontransgenic mice.

The insoluble Ab levels were found to be higher than the soluble Ab levels, and the insoluble Ab42 levels were markedly increased in mutant PS2 transgenic mice.  

Behavioral:

N/A

Availability

Not commercially available.  
Contact Dr. Yasuo Ihara 
Department of Neuropathology
University of Tokyo
7-3-1 Hongo
Bunkyo-ku, Tokyo 113-0033
Japan
Tel: 81-3-5841-3541
Fax: 81-3-5800-6852
yihara@m.u-tokyo.ac.jp

Patents: None

Reference

Primary:

Oyama F, Sawamura N, Kobayashi K, Morishima-Kawashima M, Kuramochi T, Ito M, Tomita T, Maruyama K, Saido TC, Iwatsubo T, Capell A, Walter J, Grunberg J, Ueyama Y, Haass C, Ihara Y. Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid beta-protein 42 in the brain. J Neurochem 1998 Jul;71(1):313-22. Abstract.

Associated:

Sawamura N, Morishima-Kawashima M, Waki H, Kobayashi K, Kuramochi T, Frosch MP, Ding K, Ito M, Kim TW, Tanzi RE, Oyama F, Tabira T, Ando S, Ihara Y. Mutant presenilin 2 transgenic mice. A large increase in the levels of Abeta 42 is presumably associated with the low density membrane domain that contains decreased levels of blycerophospholipids and sphingomyelin. J Biol Chem 2000 Sep 8;275(36):27901-8. Abstract.