These Slc10a2 knock-out mice exhibit abnormalities in bile acid levels, function, and composition.
Paul A. Dawson, Wake Forest University Sch of Medicine
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Male pups tend to be smaller in size than female pups prior to weaning. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of the distal small intestine. Ileal brush border membrane vesicles isolated from homozygotes do not exhibit sodium ion dependent taurocholate uptake, indicating a loss of sodium bile acid cotransporter activity. Total plasma cholesterol levels are slightly higher than normal. Total bile acid pool size is reduced approximately 80% in homozygous mutants, although intestinal lipid absorption is reduced by only about 10%. Bile acid functional turnover rate (daily fecal bile acid excretion/pool size) is elevated 150 fold in male mutants and 75 fold in female mutants. Fecal bile acid excretion is increased 24 fold in male mutants and 11 fold in female mutants. Bile acid composition is abnormal. Fecal lipid excretion of total fat, fatty acid and neutral sterols is increased approximately 4 fold. Cholesterol absorption in the intestine is reduced by 26% in male mutants and 15% in female mutants. Cholesterol 7 alpha hydroxylase activity is increased by 2.7 fold in males and 5.2 fold in females homozygous for the mutant allele. Hepatic bile acid synthesis is increased and total hepatic cholesterol and cholesteryl ester levels are reduced. This mutant mouse strain may be useful in studies of cholesterol, lipoprotein and bile acid metabolism, and primary bile acid malabsorption.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3 and the splice acceptor site of exon 4. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice. Heterozygotes were bred to generate homozygotes.
|Allele Name||targeted mutation 1, Paul A Dawson|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Asbt-; Slc10a2-/-|
|Gene Symbol and Name||Slc10a2, solute carrier family 10, member 2|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A region of the gene extending from intron 2 through to the splice acceptor site of exon 4 was replaced with a neomycin resistance cassette. Absence of gene products was confirmed by Northern blots and by immunoblots.|
|Mutations Made By|| |
Paul Dawson, Wake Forest University Sch of Medicine
This strain is maintained as a heterozygote. Male pups tend to be smaller in size than female pups prior to weaning.
When using the Slc10a2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005213 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.