These Cyp7a1 knock-out mice exhibit wasting and early mortality with a lack of bile acids, and may be of use in applications related to the study of fat and vitamin malabsorption.
Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Cyp7a1 | cytochrome P450, family 7, subfamily a, polypeptide 1 |
Heterozygous carriers of the disrupted Cyp7a1 gene are phenotypically normal, viable, and fertile. Homozygous animals appear normal at birth but most die within the first 18 days of life. The 10-15% of homozygotes that survive are fertile. Newborn animals with a homozygous mutation in the Cyp7a1 gene lack bile acids, causing fat malabsorption as manifest by severe steatorrhea (fatty stools), deficiency of fat-soluble vitamins, and wasting due to malnutrition. Approximately 40% of the homozygotes die between postnatal days 1-4; 45% between days 11-18. Vitamin supplements given to nursing mothers can prevent deaths during the early period; cholic acid supplements in the mother's diet can prevent deaths in the later period. Mutant pups born to homozygous mothers not maintained on dietary supplements are noticeably smaller than age-matched heterozygous and wild type siblings. The skin of nursing homozygotes can be dry and scaly in appearance. Nursing heterozygous and homozygous mothers and their mutant pups not treated with cholic acid develop an unusually oily coat. No immunoreactive or enzymatically active Cyp7a1 proteins are produced in homozygous mutants, but a novel "hybrid" mRNA present in heterozygous and homozygous animals is composed of sequences derived from the 5' and 3' ends of the mutated gene.
Disruption of the murine Cyp7a1 gene was carried out in AB-1 embryonic stem cells (derived from the 129S5/SvEvBrd strain) which were injected into C57BL/6J blastocysts. A neomycin cassette replaces most of exon 3, and all of exons 4 and 5 of the gene.
Allele Name | targeted mutation 1, David W Russell |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Cyp7-; CYP7A1- |
Gene Symbol and Name | Cyp7a1, cytochrome P450, family 7, subfamily a, polypeptide 1 |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 4 |
Molecular Note | A genomic fragment containing part of exon 3, exon 4 and exon 5 was replaced with a neomycin selection cassette. Activity assays on extracts of liver microsomal memebrane preparations derived from homozygous mice demonstrated that no functional protein is made from this allele. |
Mutations Made By | Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas |
This strain requires a cholic acid dietary supplement. Cholic acid is mixed and fed with milled food at the concentration 1g cholic acid/100g milled food. A vitamin supplement may also be required. Mice from the B6129F2/J colony (Stock 101045) may be used as controls. The B6129F2/J mice only provide an approximate match to this B6,129 background. Expected coat color from breeding:Black
When using the Cyp7- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002751 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Cyp7a1<tm1Rus> |
Frozen Mouse Embryo | B6;129S7-Cyp7a1<tm1Rus>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S7-Cyp7a1<tm1Rus>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S7-Cyp7a1<tm1Rus>/J | $3373.50 |
Frozen Mouse Embryo | B6;129S7-Cyp7a1<tm1Rus>/J | $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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