ORIGINPCSK9 mice were created utilizing a full-length human PSK9 cDNA with a C-terminal V5 tag expressed under the transcriptional control of a composite human albumin promoter containing a 235 bp SV40 enhancer and a 213 bp albumin promoter element. A chimeric intron was inserted between the promoter and PCSK 9 cDNA to enhance expression. The expression cassette was flanked by a 1.2 kb insulator sequence from the chicken beta-globulin gene at both the 5’ and 3’ ends of the transgene. The expression construct was injected into the pronucleus of fertilized eggs from C57BL6J/N mice and the resulting founders and their transgenic offspring were identified from tail tissue by a PCR product amplified from the insulator sequence. Transferred to Charles River under exclusive license from Pfizer Inc., in 2011.
STRAIN CODEComing Soon
MUTATION INFORMATIONProprotein convertase subtilisin/kexin type 9 (PCSK9), which is predominantly expressed in the liver, regulates cholesterol metabolism by down regulating liver LDL receptor proteins. PCSK9 is thought to function extracellularly to promote the degradation of LDL receptors, resulting in increased plasma LDL levels. The hPCSK9 transgene is principally expressed in the kidney and mRNA expression levels in the liver are low, similar to endogenous PCSK9 in wild-type mice. Hepatic expression of the murine endogenous PCSK9 is reduced in the human transgenic mice, and overall levels of total expression of PCSK9 remain similar to wild-type controls. Human PCSK9 protein in transgenic mice is secreted and results in elevation of plasma PCSK9 levels to approximately 3μg/mL, which is approximately ten times the level found in human plasma.
RESEARCH APPLICATIONCholesterol regulation
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DISCLAIMERPCSK9 mice may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc.
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Our study, presented at the 2013 Experimental Biology Conference, focuses on the phenotype and genotype comparison for C57BL/6N substrains contributing to the International Mouse Phenotyping Consortium (IMPC).
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