Posted 7 June 2005
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
Origin: (C57BL/6, DBA/2) zygotes
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.
F. Hoffmann-La Roche AG
Building 69/440 Grenzacherstr 124, CH-4070
Phone: +41 61 6870248
Fax: +41 61 688 4575
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.
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.