The mice are hemizygous for the human apolipoprotein A2 (ApoA2) gene expressed under the control of the homologous promoter (-911/+2045). They are humanized because they are deficient in mouse ApoAII following backcrosses with APOA2 Knockout mice (KO-ApoA2 described in Weng W, Breslow JL.; PNAS, 1996). KO-ApoA2 mice have been fully backcrossed into the C57BL/6 background before mating with human ApoAII transgenic mice.
ApoAII is expressed only in liver. Its plasma concentration is 70 mg/dl with chow diet (2.5 to 3 times the physiological concentration in humans), and increases up to 110 mg/dl with a high fat diet. In the fed state, mice present dyslipidemia (hypertriglyceridemia and low HDL) characteristic of the Metabolic Syndrome. Plasma HDL are decreased by 64% and triglyceride levels increased up to 20-fold, due to decreased VLDL catabolism (1, 2).
In the fasted state, similar reduction in HDL, but normal or mildly increased plasma triglycerides; presence of VLDL-remnants (1).