This SAT-1 mutant mouse strain may be useful in studies of hyperoxaluria, hyperoxalemia, nephrocalcinosis, and hypersulfaturia.
Lorne A Clarke, University of British Columbia
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although a mutant mRNA gene product is detected by RT-PCR analysis of kidney tissue, no protein activity is detected in any tissue analyzed from homozygotes. Homozygotes exhibit reduced oxalate and sulfate transport in in isolated basolateral membrane vesicles from intestine, kidney and liver; infiltration of leukocytes around renal cortical vessels; calcium oxalate crystals and stones in kidney and bladder; elevated plasma oxalate levels and urinary sulfate levels; and increased acetaminophen-induced liver toxicity. Idua, iduronidase, alpha-L-, gene product (mRNA and enzyme activity) is normal in mice homozygous for the targeted mutation.
A targeting vector containing PGK-neo cassette and herpes simplex virus thymidine kinase genes was used to disrupt 0.9kb of sequence which included exon 3 and the ATG start codon. The construct was electroporated into 129X1/SvJ (129JSv) derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into CD1 blastocysts. The resulting chimeric animals were crossed to CD1 mice. Heterozygotes were intercrossed to generation homozygotes. Upon arrival at The Jackson Laboratory the mice were crossed with C57BL/6J at least once to establish the colony.
|Allele Name||targeted mutation 1, Daniel Markovich|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Slc26a1, solute carrier family 26 (sulfate transporter), member 1|
|Strain of Origin||129X1/SvJ|
|Molecular Note||Exon 3 (containing the start codon) was replaced with a neo cassette by homologous recombination. Northern blot analysis of RNA from liver, kidney and ileum showed absence of full length RNA in homozygotes. Western blot analysis of protein from the intestines confirmed absence of the wild-type protein. The mutation was designed to avoid affecting the surrounding gene, Idua, absence of an effect was confirmed by RT-PCR and enzyme activity analyses.|
|Mutations Made By|| |
Lorne Clarke, University of British Columbia
When maintaining a live colony, these mice can be bred as homozygotes.
When using the STOCK Slc26a1tm1Mark/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012892 in your Materials and Methods section.