Mice homozygous for this targeted mutant allele display a proatherogenic serum lipoprotein profile characterized by elevated levels of serum and hepatic cholesterol and triglycerides. This mutant mouse strain represents a model that may be useful in studies related to bile acid and lipid homeostasis.
IMR Colony, The Jackson Laboratory
Genetic Background | Generation |
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N11F12
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Nr1h4 | nuclear receptor subfamily 1, group H, member 4 |
Mice that are homozygous for the targeted Nr1h4 allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Nr1h4 protein product is detected in liver tissue although an aberrant transcript appears to be generated. Homozygous mice display a proatherogenic serum lipoprotein profile characterized by elevated levels of serum and hepatic cholesterol and triglycerides. Serum bile acids are also elevated. When fed a diet supplemented with 1% cholic acid, severe wasting, hypothermia and increased mortality is observed. Wildtype mice fed a similar diet display no ill effects. Levels of fecal bile excretion are reduced in homozygotes. This mutant mouse strain represents a model that may be useful in studies related to bile acid and lipid homeostasis.
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.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the exon encoding the ligand-binding domain (nts 1238-1779). A loxP site was placed 5' of the targeted exon. The neomycin resistance and thymidine kinase genes were flanked by loxP sites and placed 3' of the targeted exon. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells from Genome Systems Inc. (St. Louis, MO). Correctly targeted ES cells were injected into C57BL/6N blastocysts. The resulting chimeric animals were crossed to female C57BL/6N mice. Progeny animals were mated with heterozygous transgenic mice expressing Cre recombinase (EIIA promoter) on a pure FVB background. Offspring bearing the recombined Nr1h4 allele, but not the Cre transgene were obtained. The mice were then backcrossed to C57BL/6J for 5 generations.
Allele Name | targeted mutation 1, Frank Gonzalez |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | FXR/BAR -; FXR-; Fxrtm1Gonz; FXRalpha- |
Gene Symbol and Name | Nr1h4, nuclear receptor subfamily 1, group H, member 4 |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 10 |
General Note | The ES cell line was not specified, but was purchased from Genome Systems (St. Louis, MO). (Note added 7/26/01: Genome Systems was bought by Incyte.) |
Molecular Note | Mice with a targeted deletion of the last exon encoding the ligand binding domain and all of the 3' untranslated region were produced as follows: A loxP site was inserted in the intron 5' to the last exon and a loxP-flanked neomycin cassette was inserted 3' to the last exon. After production of chimeric founder mice, F1 mice were mated to Tg(EIIa-Cre)1Lmgd mice to produce offspring that carried a recombined deletion of the last exon and neomycin cassette. No Nr1h4 protein product is detected in liver tissue from these null mice although an aberrant transcript appears to be generated. |
Mutations Made By | Frank Gonzalez, National Institutes of Health (NIH/NCI) |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the FXR/BAR- mouse strain in a publication, please cite the originating article(s) and include JAX stock #007214 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous for Nr1h4<tm1Gonz> |
Frozen Mouse Embryo | B6.129X1(FVB)-Nr1h4<tm1Gonz>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129X1(FVB)-Nr1h4<tm1Gonz>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129X1(FVB)-Nr1h4<tm1Gonz>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129X1(FVB)-Nr1h4<tm1Gonz>/J Frozen Embryo | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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