General Information

Posted 10 August 2004

Transgene:

1. Gene-targeting vector with a V642I mutation in exon 17 and floxP-TK-Neo cassettes in intron 17, / TT2 ES cells/ obtained V642I-APP knock-in mutant clone, R34.

2. R34 clone submitted to transient expression of Cre recombinase, leaving 97bp-loxP sequence and restriction sequences in intron 17. Resulting clone R34C(30)-9 used to generate mice.

Mutation: V642I APP

Mouse Strain: Origin:C57BL/6 x CBA background Chimeric males mated with CD-1 females.

Phenotype

Neuropathological Analysis:

At 27-29 months mice displayed altered regulation of Aβ production and/or metabolism, which caused an increase of Aβ42(43) against Aβ40, but without neuritic plaque formation, NFT formation, massive neuronal loss or brain atrophy.

Behavioral:

At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory slightly affected, but no deterioration in short-term working memory.

Availability

Contact:
Dr Masaaki Matsuoka
Department of Pharmacology
Keio University School of Medicine
Shinanomachi, Shinjuku-ku, Tokyo 160-8582
Phone: +81-3-5363-8428
Email: Dr Masaaki Matsuoka

Patents:

US Patent Application No.60/482,021: Targeted Introduction of V642I Mutation in Amyloid Precursor Gene Causes Functional Abnormalities Resembling Early Stage of Alzheimer's Disease in Aged Mice Ikuo Nishimoto, Kiyoshi Kurokawa, Toshio Miyata June 25, 2003. Status: pending

PCT/JP2004/002296 Neurons Created from Neuro-degenerative Disease Mutation Knock-in ES Cells by a Highly Efficient Differentiation Protocol Ikuo Nishimoto, Kiyoshi Kurokawa, Toshio Miyata Feb 26, 2004. Status: pending

References

Primary:

Kawasumi M, Chiba T, Yamada M, Miyamae-Kaneko M, Matsuoka M, Nakahara J, Tomita T, Iwatsubo T, Kato S, Aiso S, Nishimoto I and Kouyama K. Targeted introduction of V642I mutation in amyloid precursor protein gene causes functional abnormality resembling early stage of Alzheimer's disease in aged mice. Eur J Neurosci 19:2826, 2004. Abstract

Associated:

Abe, Y., Kouyama, K., Tomita, T., Tomita, Y., Ban, N., Nawa, M., Matsuoka, M., Niikura, T., Aiso, S., Kita, Y., Iwatsubo, T. & Nishimoto, I. Analysis of neurons created from wild-type and Alzheimer's mutation-knock-in ES cells by a highly efficient differentiation protocol. J. Neurosci., 23, 8513-8525, 2003. Abstract.