These BALB.LDLR knock-out mice may be useful for studying the effects of hyperlipidemia and hyperglycemia on diabetic nephrology and artherosclerosis.
Dr. Renee C LeBoeuf, Universtiy of Washington
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Ldlr | low density lipoprotein receptor |
In the BALB.LDLR-/- strain, a neomycin (neo) selection cassette is inserted in exon 4 of the low density lipoprotein receptor (Ldlr) gene, abolishing endogenous gene function. Homozygous mice are viable, fertile, appear normal in size, and do not display any gross physical or behavioral abnormalities. On a 4% diet, BALB.LDLR-/- mice have increased cholesterol (~200 mg/dl), increased triglycerides (~170mg/dl), and increased blood glucose (122 mg/dl) as compared with wildtype (WT). When moved onto a 21% fat diet these mice have cholesterol levels of 572 mg/dl, triglyceride levels of 180mg/dl, and blood glucose levels of 141 mg/dl. They exhibit renal injury, tubulointerstitial injury, and an increase in interstitial macrophages, and an increase in blood urea nitrogen when challenged with hyperlipidemia and hyperglycemia. When injected with Streptozotocin these mice also exhibit atherosclerotic lesions, aortic sinus lesions, and aortic fatty streak lesions caused by hyperlipidemia. These mice may be useful for studying the effects of hyperlipidemia and hyperglycemia on diabetic nephrology and artherosclerosis.
A targeting vector was designed to insert neomycin (neo) selection cassette into exon 4 of the low density lipoprotein receptor (Ldlr) gene, abolishing gene function. This construct was electroporated into 129S7/SvEvBrd-Hprt1+-derived AB-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric males were bred with C57BL/6 females. The resulting offspring were backcrossed to C57BL/6 for at least 10 generations to establish a colony of Ldlr-/- mice (Stock No. 002207). These mice were subsequently backcrossed to BALB/cByJ for at least 10 generations to establish a colony of BALB.LDLR-/- mice. Upon arrival at The Jackson Laboratory, mice were bred with BALB/cByJ inbred mice (Stock No. 001026) for at least one generation to establish the colony.
Allele Name | targeted mutation 1, Joachim Herz |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | LDLR-; LDLR KO; LDLr0; LDLrKO; LDLr-KO; Ldlrtm1Her |
Gene Symbol and Name | Ldlr, low density lipoprotein receptor |
Gene Synonym(s) | |
Site of Expression | Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals. |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 9 |
General Note | When used in bone marrow transplant into Ldlrtm1Her homozygous mice, Abca1tm1Jdm Abcg1tm1Dgen 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. |
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. |
Mutations Made By | Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas |
When maintaining a live colony, homozygous mice may be bred together.
When using the CByJ.129S7(B6)-Ldlrtm1Her/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012845 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Ldlr<tm1Her> |
Frozen Mouse Embryo | CByJ.129S7(B6)-Ldlr<tm1Her>/J | $2595.00 |
Frozen Mouse Embryo | CByJ.129S7(B6)-Ldlr<tm1Her>/J | $2595.00 |
Frozen Mouse Embryo | CByJ.129S7(B6)-Ldlr<tm1Her>/J | $3373.50 |
Frozen Mouse Embryo | CByJ.129S7(B6)-Ldlr<tm1Her>/J | $3373.50 |
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