The Tg2576 strain is a mouse model for AD in which the transgene is the human 695 splice-variant of APP that contains the double mutation K670M, N671L driven by a hamster prion protein gene promoter (expression is predominantly in neurons). The brains of these animals contain about five times more transgenic mutant human APP than endogenous mouse APP. Transgenic APP expression appears to remain unchanged between 2 and 14 months of age. They exhibit about a fivefold increase in Ap40 and a 10- to 15-fold increase in Ap42/43 over levels measured in nontransgenic littermates. Similar to observations in AD brain, and consistent with the notion that elevated Ap is potentially toxic to brain cells, senile plaques in the brains of these mice are associated with signs of cellular inflammatory responses.
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