General Information

Transgene: The Swedish familial AD double mutation (SFAD, K670N, M671L substitutions) was introduced by site-directed mutagenesis into cDNA encoding h βAPP₇₅₁. The Thy-1.2-hAPP751SFAD transgene was generated by insertion of the 2.4 kb hAPP751 SFAD cDNA fragment into the XhoI site of an expression vector containing mouse Thy1.2 glycoprotein gene and promoter. The 1.5 kb BanI-XhoI fragment encompassing exons 2 and 4 was replaced by the XhoI cloning site. Vector-free linear fragments, carrying Thy1-huAPP₇₅₁SFAD were microinjected into pronuclei of B6D2F1 zygotes. After microinjection, viable zygotes were implanted into the oviducts of pseudopregnant foster mothers. Transgenic founders were crossed to C57BL/6 to establish lines.

Mutation: Human APP K670N, M671L

Promoter: mThy1.2

Origin: (C57BL/6, DBA/2) zygotes

Phenotype

Neuropathological analysis:

Amyloidosis in the 2nd year of life: Levels of Aβ lower than 1ng/mg wet brain at 12 month. At 24 months, presence of congophilic plaques in cortex and hippocampus, Aβ40 levels of about 200ng/mg wet brain measured after urea extraction, Aβ42 levels measured in the same conditions 10 fold lower - Amyloidosis 4X more prominent in females than males.

Availability

Laurence Ozmen
F. Hoffmann-La Roche AG
Building 69/440 Grenzacherstr 124, CH-4070
Basel, Switzerland
Phone: +41 61 6870248
Fax: +41 61 688 4575
Email: Laurence.ozmen@roche.com

Reference

Primary:

J.G. Richards, G.A. Higgins, A.M. Ouagazzal, L. Ozmen, J.N. Kew, B. Bohrmann, P. Malherbe, M. Brockhaus, H. Loetscher, C. Czech, G. Huber, H. Bluethmann, H. Jacobsen and J.A. Kemp. PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation, J. Neurosci. 23:8989-9003, 2003. Abstract.

Associated:

von Kienlin M, Künnecke B, Metzger F, Steiner G, J. Richards G, Ozmen L, Jacobsen H, Loetscher H. Altered metabolic profile in the frontal cortex of PS2APP transgenic mice, monitored throughout their life span. Neurobiology of Dis. 18(1):32-39, 2005. Abstract.