D2.129S7(B6)-Ldlr^tm1Her/J

Stock number: 007068
Research areas: Cardiovascular Research, Diabetes and Obesity Research, Internal/Organ Research, Metabolism Research, Mouse/Human Gene Homologs

Description

Mice homozygous for this Ldlr (low density lipoprotein receptor) targeted mutation, Ldlr^tm1Her, may be useful for studying lipid and leptin homeostasis, hyperglycemia, hypercholesterolemia, atherosclerosis, and the effects of diet on skin and coat.

Detailed description

Mice homozygous for the Ldlr^tm1Her mutation have an elevated serum cholesterol level of 200-400 mg/dl and they have very high levels (>2,000 mg/dl) when fed a high fat diet. Normal serum cholesterol in the mouse is 80-100 mg/dl. This mutant mouse strain may be useful in studies of lipid and leptin homeostasis, hyperglycemia, hypercholesterolemia, atherosclerosis, and the effects of diet on skin and coat.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 4. The construct was electroporated into 129S7/SvEvBrd-Hprt1⁺ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6J for 10 generations. These B6.129S7-Ldlr^tm1Her/J (Stock No. 002207) mice were then backcrossed to DBA/2J (Stock No. 000671) using a speed congenic protocol to produce this strain.

Allele

Symbol: Ldlr^tm1Her
Name: targeted mutation 1, Joachim Herz
MGI accession ID: MGI:1857212
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ldlr
Marker name: low density lipoprotein receptor
Chromosome: 9
Strain of origin: 129S7/SvEvBrd-Hprt⁺
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.