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Strain Name:

B6.129S7-Ldlrtm1Her/J

Stock Number:

002207

Availability:

Level 2

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General Terms and Conditions

Genes & Alleles   Ldlr;   Ldlrtm1Her;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain 129S7 via AB1 ES cell line (+Hprt-bm2)
Donating Investigator IMR Colony,   The Jackson Laboratory
GenerationN10F32 (03-JAN-08)

Appearance
black
Related Genotype: a/a

Strain Description
Mice homozygous for the Ldlrtm1Her 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.

Strain Development
The Ldlrtm1Her mutant strain was developed in the laboratory of Dr. Robert Hammer and Dr. Joachim Herz at the Howard Hughes Medical Institute Research Laboratories, University of Texas Southwestern Medical Center at Dallas. The 129-derived AB1 ES cell line was used. The strain has been backcrossed to C57BL/6J mice for 10 generations (N10).

Related Disease (OMIM) Terms

Hypercholesterolemia, Autosomal Dominant
Mammalian Phenotype Terms assigned by genotype

Ldlrtm1Her/Ldlrtm1Her

        B6.129S7-Ldlrtm1Her
  • homeostasis/metabolism phenotype
  • decreased circulating HDL cholesterol level (J:130794)
    • when fed a high-cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for HDL of 0.77 compared to 0.83 in wild type mice
  • decreased circulating interleukin-10 level (J:130794)
  • increased circulating LDL cholesterol level (J:130794)
    • when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for LDL of 0.88 compared to 0.84 in wild type mice
  • increased circulating VLDL cholesterol level (J:130794)
    • when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for VLDL of 0.92 compared to 0.88 in wild type mice
  • cardiovascular system phenotype
  • increased susceptibility to atherosclerosis (J:130794)
    • mice exhibit extensive intimal thickening and 60% to 80% of the aortic surface is sudanophilic unlike in wild type mice
    • mice exhibit endothelial disruption and an accumulation of macorphage and foam cells at the site of atherosclerotic plaques
  • immune system phenotype
  • decreased circulating interleukin-10 level (J:130794)

Ldlrtm1Her/Ldlrtm1Her

        B6.129S7-Ldlrtm1Her/J
  • homeostasis/metabolism phenotype
  • decreased triglyceride level (J:85174)
    • when fed regular chow or a high fat diet for 16 weeks, serum triglyceride levels are decreased compared to similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes
  • increased cholesterol level (J:85174)
    • when fed a high fat diet, mice exhibit an increase in cholesterol content in the adrenal gland
    • when fed a high fat diet, mice exhibit a greater increase in liver cholesterol content (11-fold) compared to in similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes (2.5-fold)
    • increased circulating cholesterol level (J:85174)
      • whether are fed a high fat diet or regular chow, plasma cholesterol levels are increased relative to similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes
      • when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlrtm1Her homozygotes (3-fold)
      • increased circulating HDL cholesterol level (J:85174)
        • when fed regular chow or a high fat diet for 16 weeks, serum HDL levels are increased compared to similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes
      • increased circulating LDL cholesterol level (J:85174)
        • when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlrtm1Her homozygotes (3-fold)
      • increased circulating VLDL cholesterol level (J:85174)
        • when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlrtm1Her homozygotes (3-fold)
  • liver/biliary system phenotype
  • abnormal liver morphology (J:85174)
    • when fed a high fat diet, mice exhibit larger diameter and more frequent lipid droplets than in Apoa1tm1Unc Ldlrtm1Her homozygotes
  • endocrine/exocrine gland phenotype
  • abnormal adrenal gland morphology (J:85174)
    • when fed a high fat diet, mice exhibit an increase in cholesterol content in the adrenal gland
  • skin/coat/nails phenotype
  • alopecia (J:85174)
    • when fed a high fat diet
  • scaly skin (J:85174)
    • when fed a high fat diet
  • thick skin (J:85174)
    • when fed a high fat diet

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Ldlrtm1Her/Ldlrtm1Her

        Background Not Specified
  • homeostasis/metabolism phenotype
  • increased circulating cholesterol level (J:84694)
    • increased circulating LDL cholesterol level (J:84694)
      • on a chow diet, plasma LDL levels were higher than both those of wild type mice and Ldlrap1tm1Her homozygous mutant mice

Ldlrtm1Her/Ldlrtm1Her

        involves: 129S7/SvEvBrd * C57BL/6
  • homeostasis/metabolism phenotype
  • increased circulating LDL cholesterol level (J:102291)
    • clearance of 125I-LDL from circulation is retarded, uptake of DiI-LDL by hepatocytes is decreased, and uptake of 3H-CE-LDL by the liver is lower compared to wild type

Ldlrtm1Her/Ldlrtm1Her

        involves: 129S7/SvEvBrd
  • homeostasis/metabolism phenotype
  • increased circulating LDL cholesterol level (J:114949)
    • male mice have a marked increase in plasma LDL cholesterol compared to wild type
    • in wild type mice parabiosed with Ldlr-null mice (resulting in shared circulation), plasma total cholesterol levels did not increase significantly over pre-surgery levels

Ldlrtm1Her/Ldlrtm1Her

        involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6
  • cardiovascular system phenotype
  • atherosclerotic lesions (J:96110)
    • atherosclerosis in both aortic arch and descending aorta
  • homeostasis/metabolism phenotype
  • increased circulating cholesterol level (J:96110)
    • hypercholesterolemic

Gene & Allele Details

Allele Symbol Ldlrtm1Her
Allele Name targeted mutation 1, Joachim Herz
Common Name(s) LDLR KO; LDLR-; LDLr0; LDLrKO; Ldlrtm1Her;
Mutation Made By Joachim Herz,   Univ of Texas Southwest Med Ctr Dallas
Strain of Origin129S7/SvEvBrd-Hprt1<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name Ldlr, low density lipoprotein receptor
Chromosome 9
Gene Common Name(s) FH; FHC; LDLRA;
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. [J:37394]

Control Information

  Allele   Control
 Ldlrtm1Her  000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Ldlr tm1Her

Colony Maintenance

Breeding & HusbandryThis Ldlrtm1Her strain is maintained by mating homozygous siblings. Only homozygous mice may be ordered.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Ldlrtm1Her     (11 strains)

Strains carrying other alleles of Ldlr
005061   C57BL/6J-LdlrHlb301/J
View Strains carrying other alleles of Ldlr     (1 strain)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report
JAX Notes, Fall 2003; 491. JAX West Expansion

Animal Health Reports

Room Number           AX1

Research Applications

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Obesity With Diabetes (diet-induced)

Ldlrtm1Her related

Cardiovascular Research
Atherosclerosis
Hypercholesterolemia

Metabolism Research
Lipid Metabolism

Mouse/Human Gene Homologs
hypercholesterolemia, familial

References

Selected Reference(s)

Ishibashi S; Brown MS; Goldstein JL; Gerard RD; Hammer RE; Herz J. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery [see comments] J Clin Invest 92(2):883-93. [PubMed: 8349823]  [J:37394]

Additional References

Price and Supply Information

Strain Name: B6.129S7-Ldlrtm1Her/J
Stock Number: 002207

Price Details

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Supply Details

Standard SupplyLevel 2. Colony sized for average order of 10-80 mice. Larger quantities or custom orders arranged upon request.
Supply Notes Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available.
Strains that must be genotyped are not available until five to seven weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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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.
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