C57BL/6N-Tg(ALB-PCSK9)APfzr/J

Stock number: 031577
Product name: hPCSK9
Research areas: Cardiovascular Research

Description

hPCSK9 mice express a human PCSK9 gene under direction of the human albumin promoter. Mice are associated with the regulation and degradation of liver low density lipoprotein receptor (LDLR) proteins.

Detailed description

hPCSK9 mice express a human proprotein convertase subtilisin/kexin type 9 (PCSK9) cDNA under direction of a human albumin (ALB) promoter. PCSK9 is an enzyme expressed in liver, and to a lesser extent in the intestine and kidney, that regulates cholesterol metabolism by down regulating liver LDL receptor (LDLR) proteins through proteasomal degradation. The hPCSK9 mice have increased human PCSK9 mRNA levels in kidney, and no endogenous PCSK9 mRNA is evident in the kidney. The level of human PCSK9 mRNA in the liver is low, slightly higher than endogenous levels. Mice exhibit a reduction of liver LDLR which leads to increases in plasma total cholesterol, LDL cholesterol, and apolipoprotein B. These figures are further increased by a high fat, high cholesterol diet.

Development

The hPCSK9 transgenic construct contains a composite human albumin (ALB) promoter, containing a 235-bp SV40 enhancer element and a 213-bp albumin promoter element, directing expression of human proprotein convertase subtilisin/kexin type 9 (PCSK9) cDNA, followed by a C-terminal V5 tag. A chimeric intron (from pRL-SV40) was inserted between the promoter and PCSK9 cDNA to enhance expression. The linearized construct was microinjected into fertilized C57BL/6NJ oocytes. hPCSK9 mice, from founder line A, were bred to and maintained on the C57BL/6NJ genetic background. Cryopreserved sperm was shipped to The Jackson Laboratory. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

Of note, historical review of The Jackson Laboratory colony breeding results suggest that the transgene may be integrated on the X chromosome. Additional investigation to verify this has not been attempted or reported [March 2021].

Allele

Symbol: Tg(ALB-PCSK9)APfzr
Name: transgene insertion A, Jeffrey Stock
MGI accession ID: MGI:6144026
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: hPCSK9
Marker symbol: Tg(ALB-PCSK9)APfzr
Marker name: transgene insertion A, Jeffrey Stock
Chromosome: UN
Strain of origin: C57BL/6N
Expressed genes: PCSK9,proprotein convertase subtilisin/kexin type 9,human
Site of expression: Kidney
Molecular note: The transgenic construct contains a composite human albumin (ALB) promoter, containing a 235 bp SV40 enhancer element and a 213 bp albumin promoter element, directing expression of human proprotein convertase subtilisin/kexin type 9 (PCSK9) cDNA, followed by a C-terminal V5 tag. A chimeric intron (from pRL-SV40) was inserted between the promoter and PCSK9 cDNA to enhance expression. The transgene expresses primarily in the kidney.