The single point mutation (LdlrHlb301) in this ENU mutagenized strain was originally named "Wicked High Cholesterol" (WHC) for a phenotype of elevated atherosclerotic lesion formations and reduced hepatosteatosis following an atherogenic diet. This mutant mouse strain may be useful in studies of familial hypercholesterolemia and atherosclerosis.
Read More +Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Chemically induced (ENU) | Ldlr | low density lipoprotein receptor |
Mice that are homozygous for the mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This single base pair G to A transition mutation in exon 14, nucleotide 2096 was induced by ENU mutagenesis. The "Wicked High Cholesterol" (WHC) phenotype was mapped to the Ldlr, low density lipoprotein receptor, gene. Although total plasma cholesterol levels do not differ between sexes, when fed a standard chow diet for 5 weeks, homozygous WHC males exhibit higher triglyceride and HDL levels than homozygous WHC females. When fed Western diet for 5 weeks, mutant WHC males exhibit higher HDL levels than female WHC mutants. When fed an atherogenic diet for 5 weeks, WHC homozygotes of both sexes develop elevated total cholesterol levels of more than a 4 fold increase when compared to WHC homozygotes on standard chow diet. Cholesterol and HDL levels of WHC homozygotes fed atherogenic diet for 5 weeks remain elevated 1 month after resuming chow diet. Atherosclerotic lesions develop in WHC homozygotes fed Western and atherogenic diet, with the largest lesions observed in homozygous WHC mice fed the atherogenic diet. Long term (34 weeks) atherogenic diet consumption results in formation of multiple cutaneous xanthomas in the distal limbs of WHC homozygotes, 42 weeks of age. Half of the WHC homozygotes develop gallstones.
On the atherogenic diet WHC homozygotes develop significantly greater HDL and triglyceride levels, as well as larger atherosclerotic lesions, when compared to mice carrying the Ldlr targeted mutation (Stock No. 002207).
This mutant mouse strain may be useful in studies of familial hypercholesterolemia and atherosclerosis.
Following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice (Stock No. 000664), a forward genetic screen was utilized to identify phenotypic deviants in complex heart, lung, blood, and sleep disorders, at the Mouse Heart, Lung, Blood, and Sleep Disorders (HLBS) Center at The Jackson Laboratory.
Screening of third generation mice (G3) identified mice with elevated total plasma cholesterol levels after being fed an atherogenic diet for 5 weeks. The "Wicked High Cholesterol" (WHC) phenotype was mapped to chromosome 9. Sequencing of the candidate gene Ldlr, low density lipoprotein receptor, revealed a G to A transition in exon 14, nucleotide 2096; missense mutation C699Y. Heterozygotes were crossed to generate homozygotes. The mice have been maintained on a C57BL/6J background.
Allele Name | heart, lung and blood 301 |
---|---|
Allele Type | Chemically induced (ENU) |
Allele Synonym(s) | WHC; wicked high cholesterol |
Gene Symbol and Name | Ldlr, low density lipoprotein receptor |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 9 |
General Note | Schmidt and Kostner (Atherosclerosis 148(2):431-432, 1999) identified the same mutation in an Austrian patient with Familial Hypercholesterolemia (FH): a G-to-A transition at nucleotide 2093 of the human LDLR coding sequence, resulting in replacement of cysteine with tyrosine at amino acid 677 (count does not include 21-aa signal peptide). |
Molecular Note | This phenotypic mutation was identified in a screen of the progeny of ENU treated male mice for serum cholesterol elevation in response to a high fat, high cholesterol diet. It is a G to A transition at nucleotide 2096 of the mouse cDNA sequence, in a region encoded by exon 14, resulting in replacement of a highly conserved cysteine by tyrosine at amino acid 699 (C699Y; count includes 21-aa signal peptide), which is predicted to cause a folding defect and failure of the protein to transit from the endoplasmic reticulum to the Golgi system. |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the WHC mouse strain in a publication, please cite the originating article(s) and include JAX stock #005061 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Ldlr<Hlb301>, 1 pair minimum |
Frozen Mouse Embryo | C57BL/6J-Ldlr<Hlb301>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | C57BL/6J-Ldlr<Hlb301>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | C57BL/6J-Ldlr<Hlb301>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | C57BL/6J-Ldlr<Hlb301>/J Frozen Embryos | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.