Basic Information
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Gene Targeting Strategy
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The exons 1-12 of mouse Pcsk9 gene that encode the full-length protein were replaced by human PCSK9 exons 1-12 in B-hPCSK9 mice.
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mRNA Expression Analysis
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Species-specific PCSK9 gene expression analysis in wild-type and humanized B-hPCSK9 mice by RT-PCR. Murine Pcsk9 mRNA was detected in liver isolated from wild-type (+/+) mice, while human PCSK9 mRNA was detected exclusively in homozygous B-hPCSK9 mice.
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Protein Expression Analysis
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Species-specific PCSK9 protein expression analysis in humanized B-hPCSK9 mice. Serum was collected from wild-type (+/+) and homozygous B-hPCSK9 (H/H) mice, and analyzed using species-specific PCSK9 ELISA kits. Murine PCSK9 protein was detected in wild-type mice, while human PCSK9 protein was exclusively detected in B-hPCSK9 mice.
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Lipid Metabolism Analysis in Humanized B-hPCSK9 Mice
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Lipid metabolism analysis in humanized B-hPCSK9 mice. Plasma concentrations of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in wild-type C57BL/6 and B-hPCSK9 mice (n = 36, 6-week-old) were analyzed. Similar concentrations of TG, TC, LDL-C and HDL-C were observed between wild-type and B-hPCSK9 mice.
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In vivo Efficacy of Anti-Human PCSK9 Antibodies in Humanized B-hPCSK9 Mice
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Anti-human PCSK9 antibodies improved lipid metabolism in humanized B-hPCSK9 mice. Wild-type C57BL/6 and B-hPCSK9 male mice fed a western diet (WD) were treated with Alirocumab (in house)/Evolocumab (in house) or isotype control antibody (single dose, s.c.) (n = 8) to evaluate LDL-C and total cholesterol concentrations. Blood was collected on Day -5, 1, 3, 5 and 8 for analysis. Serum levels of (A) LDL-C and (B) TC were reduced in mice treated with anti-human PCSK9 antibodies compared to the isotype control. Results indicated that anti-human PCSK9 antibodies effectively controlled blood lipid concentrations in male B-hPCSK9 mice. Values are expressed as mean ± SEM. TC, total cholesterol; LDL-C, low density lipoprotein cholesterol.
