Ctr1flox floxed mutant mice may be useful for studying the physiological role of CTR1 in Cu homeostasis.
Dennis Thiele, Duke University School of Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), No functional change) | Slc31a1 | solute carrier family 31, member 1 |
Ctr1flox 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 Ctr1int/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.
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 Ctr1flox 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 Name | targeted mutation 2, Dennis J Thiele |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | Ctr1flox |
Gene Symbol and Name | Slc31a1, solute carrier family 31, member 1 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 4 |
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. |
When maintaining a live colony mice homozygous for the floxed allele may be bred together.
When using the STOCK Slc31a1tm2Djt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025651 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Slc31a1<tm2Djt> |
Frozen Mouse Embryo | STOCK Slc31a1<tm2Djt>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Slc31a1<tm2Djt>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Slc31a1<tm2Djt>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Slc31a1<tm2Djt>/J Frozen Embryo | $3373.50 |
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