Homozygotes have reduced plasma cholesterol levels and accelerated clearance of circulating cholesterol. This strain may be useful in studies of lipid homeostasis, cholesterol metabolism, apolipoprotein function, and statin treatment for hypercholesterolemia.
Dr. Jay D. Horton, Univ of Texas SW Med Center at Dallas
Homozygous mice are viable and fertile with no behavioral abnormalities. No expression of the endogenous RNA or protein is observed in liver. Homozygotes have reduced plasma cholesterol levels; apolipoprotein B (apoB)-containing low-density liproprotein (LDL) is nearly undetectable and apolipoprotein E (apoE)-containing high density liproprotein (HDL) levels are reduced 30%. Homozygotes show increased hepatic LDL-receptor (LDLR) protein (but not RNA) expression. Homogygous mice also have accelerated clearance of circulating cholesterol. Lovastatin addition to the diet of homozygous mice results in further increased hepatic LDLR and LDL clearance from the blood. Heterozygous mice have intermediate plasma cholesterol and LDL clearance. This mouse may be useful in studies of lipid homeostasis, cholesterol metabolism, apolipoprotein function, and statin treatment for hypercholesterolemia.
A targeting vector was designed to replace the region spanning from the C-terminal region of exon 2 through exon 4 of the endogenous gene with a neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived SM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females. Heterozygous offspring were crossed to generate homozygous mice.
|Allele Name||targeted mutation 1, Jay D Horton|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pcsk9, proprotein convertase subtilisin/kexin type 9|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A targeting vector containing a neomycin resistance gene was inserted to replace the 3' half of exon 2 through exon 4. Northern blot of mutant livers confirmed absence of transcript. Immunoblot of livers further confirmed absence of protein.|
|Mutations Made By|| |
Dr. Jay Horton, Univ of Texas SW Med Center at Dallas
When maintaining a live colony, homozygous mice may be bred together.
When using the Pcsk9- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005993 in your Materials and Methods section.