These IRlox mutant mice have loxP sites flanking exon 4 of the targeted gene. When bred to Cre-recombinase expressing mice, offspring will have a deletion of exon 4 in the cre expressing tissue(s). These floxed mice may be useful in studying insulin receptor function in several different tissues (including pancreas, liver, and skeletal muscle), as well as diabetes and glucose regulation.
C. Ronald Kahn, Joslin Diabetes Center
Mice homozygous for this IRlox allele are viable and fertile. These mutant mice have loxP sites flanking exon 4 of the targeted gene. When bred to Cre-recombinase expressing mice, offspring will have a deletion of exon 4 in the cre expressing tissue(s). These "floxed" mice may be useful in studying insulin receptor function in several different tissues (including pancreas, liver, and skeletal muscle), as well as diabetes and glucose regulation.
For example, when crossed to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain may be useful in studies of glucose homeostasis.
When crossed to a strain expressing Cre recombinase in skeletal and cardiac muscle (see Stock No. 006475), this mutant mouse strain may be useful in studies of diabetes.
When crossed to a strain expressing Cre recombinase in the liver (see Stock No. 003574), this mutant mouse strain may be useful in studies of insulin resistance.
When crossed to a strain expressing Cre recombinase in pancreatic beta cells (see Stock No. 003573), this mutant mouse strain may be useful in studies of diabetes.
A targeting vector was designed to insert a loxP-flanked neomycin cassette downstream of exon 4, as well as a single loxP site 80 bp downstream of exon 4 of the targeted gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. ES cell were transiently transfected with a Cre-recombinase plasmid to delete the selection cassette, leaving single loxP sites upstream and downstream of exon 4. Correctly targeted ES cells were injected into C57BL/6J blastocysts, which were injected into pseudopregnant CD-1 foster females. The resulting mutant mice (IRlox) were backcrossed to C57BL/6J inbred mice. At some point, mice were bred to Mck-Cre transgenic mice (FVB genetic background, see Stock No. 006405). The double mutants were backcrossed for 10 generations to C57BL/6 mice and then selected for the IRlox (and against the transgene) prior to arrival at The Jackson Laboratory.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Ronald Kahn|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||targeted mutation 1, Ronald Kahn; Insrtm1Khn|
|Gene Symbol and Name||Insr, insulin receptor|
|Gene Synonym(s)||RIKEN cDNA 4932439J01 gene; D630014A15Rik; D630014A15Rik; HHF5; RIKEN cDNA D630014A15 gene; IR-A; CD220; 4932439J01Rik; IR; IR-B; 4932439J01Rik|
|Strain of Origin||129S4/SvJae|
|General Note||In conjunction with Tg(Mycha-cre)1Abel, this allele is knocked out specifically in cardiac muscle. The resulting mice are referred to as "Cardiac-specific insulin receptor knockout mice" or CIRKO.
In conjunction with Tg(Ckmm-cre)5Khn, this allele is disrupted specifically in skeletal muscle. The resulting mice are referred to as "Muscle-specific insulin receptor knockout mice" or MIRKO.
|Molecular Note||Exon 4 was left flanked by single loxP sites after a downstream floxed neo cassette was removed via in vitro cre mediated recombination. Deletion of the resultant floxed fragment will result in a frameshift mutation that introduces a stop codon. Translation, if it were to occur, would putatively produce a truncated peptide consisting of 308 amino terminal residues and lacking the high affinity binding site, transmembrane domain, and kinase domain.|
|Mutations Made By|| |
C. Ronald Kahn, Joslin Diabetes Center
When maintaining a live colony, homozygous mice are bred.
When using the IRLox mouse strain in a publication, please cite the originating article(s) and include JAX stock #006955 in your Materials and Methods section.
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