129-Slc10a2^tm1Pda/J

Stock number: 005213
Product name: Slc10a2-
Research areas: Cardiovascular Research, Metabolism Research

Description

These Slc10a2 knock-out mice exhibit abnormalities in bile acid levels, function, and composition.

Detailed description

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.

Development

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

Symbol: Slc10a2^tm1Pda
Name: targeted mutation 1, Paul A Dawson
MGI accession ID: MGI:2676307
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc10a2
Marker name: solute carrier family 10, member 2
Chromosome: 8
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.