These Hsd3b7 knockout mice may be useful for studying cholesterol and bile acid biosynthesis and homeostasis.
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) | Hsd3b7 | hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7 |
These Hsd3b7-/- mice lack exons 1-6 of the hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7 (Hsd3b7) gene, abolishing gene expression. Hsd3b7 encodes an oxidoreductase which catalyzes two reactions required for the synthesis of bile acids from cholesterol in the small intestines and liver. Mutations of Hsd3b7 have been implicated in recessive forms of neonatal liver failure. Heterozygotes are viable, fertile, and normal in size. Homozygotes exhibit reduced growth and decreased survival; 45% of mice die during the first 4 days of life, and another 45% die between 8 and 18 days of age when maintained on a normal chow diet. These mice exhibit decreased intestinal cholesterol absorption, serum triglyceride levels, and cholesterol biosynthesis in the kidney. They also exhibit slight increases in fecal bile acid and steroid secretion, and increased cholesterol biosynthesis in the liver and small intestine. Hepatic fatty acid biosynthesis and triglyceride levels are also increased. These homozygous mice have oily fur and scaly skin. When mice are maintained on vitamin and bile acid supplements for the first 28 days of life, these mice appear normal and have decreased serum triglyceride levels and increased hepatic triglyceride levels when compared to wildtype controls.
A targeting construct was designed to replace exons 1-6 of the hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7 (Hsd3b7) gene with an ACN cassette. The ACN cassette, containing the neomycin resistance gene and Cre recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by loxP sites. Cre-mediated recombination during spermatogenesis removed the cassette leaving one loxP site. This construct was electroporated into 129S/SvEv-derived I1C embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females and were maintained on a mixed background. Upon arrival at The Jackson Laboratory Repository, mutant mice were bred to C57BL/6J (Stock No. 000664) mice for at least one generation.
Allele Name | targeted mutation 1 David W Russell |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Hsd3b7- |
Gene Symbol and Name | Hsd3b7, hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7 |
Gene Synonym(s) | |
Strain of Origin | 129S/SvEv |
Chromosome | 7 |
General Note | ES cell line = I1C. |
Molecular Note | Exons 1-6 were replaced by the ACN cassette encoding neomycin resistance and cre recombinase. Passage through the germline resulted in the deletion of the cassette, leaving a single loxP site. Protein was not detected in immunoblot of mutants. |
Mutations Made By | Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator reports almost complete postnatal lethality in homozygotes due to increased bile acid accumulation.
When using the B6;129S-Hsd3b7tm1Rus/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017979 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Hsd3b7<tm1Rus> |
Frozen Mouse Embryo | B6;129S-Hsd3b7<tm1Rus>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S-Hsd3b7<tm1Rus>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S-Hsd3b7<tm1Rus>/J | $3373.50 |
Frozen Mouse Embryo | B6;129S-Hsd3b7<tm1Rus>/J | $3373.50 |
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