PCSK9 is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. The LDLR, on liver and other cell membranes, binds and initiates ingestion of LDL-particles from extracellular fluid into cells, thus reducing LDL particle concentrations. PCSK9 binds to the receptor for LDL, If PCSK9 is blocked, more LDLRs are recycled and are present on the surface of cells to remove LDL-particles from the extracellular fluid. Therefore, blocking PCSK9 can lower blood LDL-particle concentrations. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. The first two PCSK9 inhibitors, alirocumab and evolocumab, were approved as once every two week injections, by the U.S. Food and Drug Administration in 2015 for lowering LDL-particle concentrations when statins and other drugs were not sufficiently effective or poorly tolerated.
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.
Protein expression analysis
Strain specific PCSK9 expression analysis in heterozygous B-hPCSK9 mice by ELISA.
Serum was collected from wild-type mice (+/+) and heterozygous B-hPCSK9 mice (H/+), and analyzed by ELISA with species-specific PCSK9 ELISA kit. Mouse PCSK9 was detectable in wild-type mice and heterozygous B-hPCSK9 mice. Human PCSK9 was exclusively detectable in heterozygous B-hPCSK9 mice but not in wild-type mice. ND: not detected.