STOCK Slc31a1^tm2Djt/J

Stock number: 025651
Research areas: Cell Biology Research, Metabolism Research

Description

Ctr1^flox floxed mutant mice may be useful for studying the physiological role of CTR1 in Cu homeostasis.

Detailed description

Ctr1^flox floxed mutant mice possess loxP sites flanking exons 1-4 of the solute carrier family 31, member 1 (Slc31a1) gene. Slc31a1 encodes Copper (Cu) transporter 1 (CTR1), a high affinity Cu⁺ transporter shown to traffic from the plasma membrane to intracellular vesicles, regulating intestinal copper absorption. Mutations in Ctr1 have been associated with diseases characterized by defects in intestinal Cu absorption and Cu distribution in the liver, e.g., Menkes disease and Wilson disease. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have loxP-flanked sequences deleted in cre-expressing tissues.

For example, when crossed to B6.SJL-Tg(Vil-cre)997Gum/J mice (Stock No. 004586) expressing Cre recombinase in intestinal epithelial cells, the resulting Ctr1^int/int mice die by three weeks of age and display hypopigmentation, skin laxity, ataxia, and brittle, kinky whiskers, as seen in patients with the human Cu⁺ homeostasis disease, Menkes kinky hair disease. They have elevated Cu⁺ levels in intestinal epithelial cells and liver, and decreased levels in heart, brain, kidney and spleen.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette downstream of exon 4, and a single loxP site upstream of exon 1 of the solute carrier family 31, member 1 (Slc31a1) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with C57BL/6J females. Offspring were bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) to delete the neo cassette. Progeny contained multiple gene rearrangments; intact floxed-exons 1-4, intact floxed-neo cassette, or excision of exons 1-4 and the neo cassette. Resulting Ctr1^flox offspring, containing only the floxed-exons, were crossed to remove the cre-expressing transgene. These mice were bred to C57BL/6J mice and were subsequently maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Slc31a1^tm2Djt
Name: targeted mutation 2, Dennis J Thiele
MGI accession ID: MGI:3771147
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Ctr1^flox
Marker symbol: Slc31a1
Marker name: solute carrier family 31, member 1
Marker synonyms: 4930445G01Rik; COPT1; CTR1; LRRGT00200; NSCT
Chromosome: 4
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A floxed neo cassette was inserted into intron 4 and an additional loxP site was inserted upstream of exon 1. The neo cassette was removed by cre-mediated recombination.