Posted 10 August 2004
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.
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.
At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial
memory slightly affected, but no deterioration in short-term working memory.
Dr Masaaki Matsuoka
Department of Pharmacology
Keio University School of Medicine
Shinanomachi, Shinjuku-ku, Tokyo 160-8582
Email: Dr Masaaki Matsuoka
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
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,
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.