These Irs4 knock-out mice exhibit impaired glucose tolerance and slight retardation in growth rate.
Gustav E. Lienhard, Dartmouth Medical School
Mice homozygous for the Irs4tm1Lhd targeted mutation are viable and fertile. However, homozygous mutant mice do appear to be at a greater risk of perinatal lethality and tend to produce fewer litters. At birth, surviving mice appear normal in size and do not display any gross physical or behavioral abnormalities. RT-PCR fails to detect Irs4 mRNA in any tissues analyzed. Growth rate appears to be slightly retarded beginning 6 weeks of age (males about 10% lighter). Homozygotes also exhibit impaired glucose tolerance, and have slightly lower blood glucose levels when compared to wildtype mice. These phenotypes are more pronounced in males than in females.
A targeting vector containing a herpes simplex virus thymidine kinase gene and a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt the single Irs4 exon. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male mice were bred to C57BL/6 females. Offspring animals were bred to homozygosity.
|Allele Name||targeted mutation 1, Gustav E Lienhard|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Irs4-; IRS-4 null|
|Gene Symbol and Name||Irs4, insulin receptor substrate 4|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette replaced the entire coding sequence of the gene except for 457 bp at the 3' end. Reverse transcription-PCR detected no mRNA expression in brain, skeletal muscle, kidney, or liver of homozygous mutant mice.|
|Mutations Made By|| |
Gustav Lienhard, Dartmouth Medical School
This strain arose on a B6;129 background and is maintained on the same. Coat color expected from breeding:Black.
When using the IRS-4 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003901 in your Materials and Methods section.