Ctr1+/- mice lack exons 1-4 of the solute carrier family 31, member 1 (Slc31a1) gene, abolishing gene function. 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. Heterozygous mice are viable and fertile, while homozygous mice die by E12.5 due to growth and developmental defects. Ctr1+/- mice express 50% the level of mRNA of both Ctr1 transcripts as control mice in liver, kidney, spleen, and brain. They also have a 50% reduction in total Cu+ levels in brain and spleen with no significant changes in liver or kidney. A slight decrease in iron levels is also seen in kidney, spleen, and brain, with a significant decrease seen in liver. Both Cu+-dependent Zn SOD activity and COX activity are reduced by 20% in brain.
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 bred to cre transgenic mice to remove the floxed exons. 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 2.1, Dennis J Thiele|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Slc31a1, solute carrier family 31, member 1|
|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 and exons 1-4 were removed by cre-mediated recombination.|
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony, or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice die by E12.5.
When using the STOCK Slc31a1tm2.1Djt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025649 in your Materials and Methods section.