129S-Slc23a2^tm1Nbm/J

Stock number: 027439
Product name: Slc23a2^-
Research areas: Cell Biology Research, Developmental Biology Research, Metabolism Research

Description

Slc23a2^- KO mice may be useful for studying the transport of ascorbic acid into tissues and across the placenta.

Detailed description

Slc23a2^- mice have a neo cassette replacing exons 10-12 of the solute carrier family 23 (nucleobase transporters), member 2 (Slc23a2) gene, abolishing gene function. Slc23a2 encodes an ascorbic acid transporter. Ascorbic acid, or Vitamin C, is required for the stability of collagen and may play a role as an antioxidant against oxidative stress. Heterozygous Slc23a2^+/- mice are viable and fertile, while, homozygous mice die soon after birth due to respiratory failure and intracerebral hemorrhage. Reduced levels of ascorbic-acid are seen in most tissues of Slc23a2^+/- newborns as compared with wild-type pups. Adult Slc23a2^+/- mice have reduced levels in the brain and blood, but not liver. Ascorbic-acid levels are undetectable in the brain, pituitary, adrenals and pancreas of Slc23a2^-/- mice, and are reduced in liver, kidney, muscle, and blood. These mice die before initial alveolar expansion, and exhibit intracranial hemorrhaging over the convex surfaces of the brain.

Development

A targeting vector was designed to replace exons 10-12 of the solute carrier family 23 (nucleobase transporters), member 2 (Slc23a2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to 129S6/SvEvTac mice. Resulting Slc23a2^- mice were maintained on a 129S6/SvEvTac background. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Slc23a2^tm1Nbm
Name: targeted mutation 1, Robert L Nussbaum
MGI accession ID: MGI:2180333
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc23a2
Marker name: solute carrier family 23 (nucleobase transporters), member 2
Chromosome: 2
Strain of origin: 129S6/SvEvTac
Molecular note: 532 nucleotides of the gene spanning exons 10-12 were replaced with a neomycin resistance cassette via homologous recombination resulting in a deletion and frameshift. RT-PCR verified the presence of mutant transcript in brain of homozygous mutant animals. Disruption of protein function was verified via ascorbic-acid uptake assay. Mouse embryonic fibroblasts from homozygous mutant animals exhibit less than 5% of normal ascorbic-acid uptake compared to wild-type.