B6;129S-Lrpap1^tm1Her Ldlr^tm1Her/J

Stock number: 002465
Product name: RAP- LDLR-
Research areas: Cardiovascular Research, Metabolism Research, Mouse/Human Gene Homologs

Description

These double KO mice are deficient in low density lipoprotein receptor-related protein and low density lipoprotein receptor.

Detailed description

Mice homozygous for both the Ldlr^tm1Her and Lrpap1^tm1Her targeted mutations are viable and fertile. They have a functional deficiency of the low density lipoprotein receptor-related protein (LRP) and low density lipoprotein receptor (LDLR). LRP is reduced in both the liver and the brain of homozygotes. They also show impaired hepatic clearance of alpha2-macroglobulin and plasma accumulation of remnant lipoproteins.

Development

This strain was developed in the lab of Dr. Joachim Herz at The University of Texas, Southwestern Medical Center at Dallas by mating Lrpap1-deficient and Ldlr-deficient mice.

Allele

Symbol: Ldlr^tm1Her
Name: targeted mutation 1, Joachim Herz
MGI accession ID: MGI:1857212
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: LDLR-; LDLR KO; LDLr0; LDLrKO; LDLr-KO; Ldlrtm1Her; Ldlr^-
Marker symbol: Ldlr
Marker name: low density lipoprotein receptor
Marker synonyms: FH; FHC; FHCL1; LDLCQ2; LDLRA
Chromosome: 9
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Site of expression: Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.
Molecular note: Insertion of a neomycin resistance cassette into exon 4. The authors predict that the targeted allele would encode a truncated non-functional protein that will not bind LDL, and that lacks a membrane spanning segment. Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.
General note: When used in bone marrow transplant into Ldlr^tm1Her homozygous mice, Abca1^tm1Jdm Abcg1^tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777)

Phenotypic Similarity to Human Syndrome: Atherosclerosis, Susceptibility to J:29950, J:225091 in mice fed a high-cholesterol diet.

Allele

Symbol: Lrpap1^tm1Her
Name: targeted mutation 1, Joachim Herz
MGI accession ID: MGI:1857214
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: RAP-
Marker symbol: Lrpap1
Marker name: low density lipoprotein receptor-related protein associated protein 1
Marker synonyms: A2MRAP; A2RAP; alpha-2-MRAP; HBP44; MRAP; MYP23; RAP
Chromosome: 5
Strain of origin: 129S7/SvEvBrd
Molecular note: A neomycin resistance cassette was inserted into sequences that encode the leader peptide. Immunoblot analysis of liver and brain did not detect the encoded protein in homozygous animals.
General note: ES cell line = JH1 or AB1 (129S7/SvEvBrd-Hprt⁺).