Apoa2 humanized transgenic mouse – line lambda

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).

Interest / Relevance: ApoAII is the second most important protein of HDL (High Density Lipoproteins) after ApoAI, and ensures HDL structural stability.
Human ApoAII promotes cholesterol efflux mediated by ABCA1 (3).
Useful for studying the role of human apo AII moderately overexpressed, and the influence of dietary and hormonal treatments (due to the presence of the homologous promoter).HDL metabolism, metabolic syndrome, insulin resistance
Keywords: ApoA2
Publications:
1- Apolipoprotein A-II/A-I ratio is a key determinant in vivo of HDL concentration and formation of pre-beta HDL containing apolipoprotein A-II. Pastier D. et al. Biochemistry 2001 40:12243-53. 2- Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism. Dugué-Pujol S. et al. J Lipid Res 2006 47:2631-9. 3- Opposite effects of plasma from human apolipoprotein A-II transgenic mice on cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells. Fournier N. et al. Arterioscler Thromb Vasc Biol 2002 22:638-43.

Reference:

RT00434

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Athina-Despina KALOPISSIS
Inserm Transfert
Research Tools
Species: Mouse
Genotype: hemizygous for human apoAII / KO-mouse apoAII
Strain: B6.Tg(hApoAII)-lambda
Genetic Background: C57BL/6
Applications: HDL metabolism, metabolic syndrome, insulin resistance
Last update: 05/12/2019

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