B6.129S6-Slc51a^tm1Pda/J

Stock number: 009082
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

These mice harbor a targeted "null" mutation of the organic solute transporter alpha (Osta) locus and may be useful in studying cholesterol metabolism, intestinal drug absorption, intestinal bile acid absorption, bile acid synthesis, and cholesterol and bile acid homeostasis.

Detailed description

Homozygous (Slc51a^-/-) mice are viable and fertile, with no mRNA or protein expression from the targeted allele. Homozygotes exhibit a small growth deficit that is ameliorated after weaning, partial impairment of intestinal bile acid absorption (impaired basolateral transport of bile acids out of the ileal epithelial cell), altered regulation of bile acid synthesis, a significantly reduced bile acid pool, intestinal lengthening and intestinal hypertrophy. Homozygous mice also have reduced hepatic Cyp7a1 expression that is inversely correlated with ileal expression of fibroblast growth factor 15 (FGF15). These mutant mice may be useful in studying cholesterol metabolism, intestinal drug absorption, intestinal bile acid absorption, bile acid synthesis, and cholesterol and bile acid homeostasis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. Although the donating investigator reports no observed phenotypic differences between Osta-mutant mice on a C57BL/6-congenic or B6;129S6 mixed genetic background, it should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace exons 1 and 2 of the targeted gene with a reverse-oriented neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Male chimera's were bred with C57BL/6J females to establish the mutant colony. Mutant mice were subsequently backcrossed to C57BL/6J for at least 8 generations prior to arrival at The Jackson Laboratory. Upon arrival, these mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. During the backcross, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Allele

Symbol: Slc51a^tm1Pda
Name: targeted mutation 1, Paul A Dawson
MGI accession ID: MGI:3778302
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc51a
Marker name: solute carrier family 51, alpha subunit
Chromosome: 16
Strain of origin: 129S6/SvEvTac
Molecular note: Exon 1 and 2 were replaced with a neo cassette. The absence of protein product was confirmed by western blot analysis on ileal extracts.