Posted 10 June 2005

General Information

Transgene: For the generation of double-transgenic mice, single-transgenic APP_V717I mice (strain FVB/N) (Moechars, D) were intercrossed with ADAM10-dn animals.

Mutation: APP_V717I

Promoter: Mouse Thy1

Mouse strain: FVB/N

Phenotype

Neuropathological Analysis:

Bigenic mice having moderate neuronal overexpression of ADAM10 showed increased secretion of the neurotrophic soluble α-secretase-released N-terminal APP domain (APPsα), reduced formation of Aβ peptides, and prevented their deposition in plaques. Functionally, impaired long-term potentiation and cognitive deficits were alleviated.

Behavioral

Improved performance in Morris Water Maze test as compared to APP_V717I mice

Availability

Not available. For information on these mice, please contact:
Falk Fahrenholz
Institute of Biochemistry
University of Mainz
Becherweg 30, D-55099 Mainz, Germany
Fax: 49-6131-392-5348
Email: bio.chemie@uni-mainz.de

References

Primary:

Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F. A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J. Clin. Invest. 113: 1456-1464, 2004. Abstract

Associated:

Moechars, D. Dewachter I, Lorent K, Reverse D, Baekelandt V, Naidu A, Tesseur I, Spittaels K, Haute CV, Checler F, Godaux E, Cordell B, Van Leuven F. Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J. Biol. Chem. 274:6483-6492, 1999. Abstract