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
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|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Hsd3b7, hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7|
|Strain of Origin||129S/SvEv|
|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.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.