B6;129-Irs4^tm1Lhd/J

Stock number: 003901
Product name: IRS-4 KO
Research areas: Diabetes and Obesity Research

Description

These Irs4 knock-out mice exhibit impaired glucose tolerance and slight retardation in growth rate.

Detailed description

Mice homozygous for the Irs4^tm1Lhd 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.

Development

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

Symbol: Irs4^tm1Lhd
Name: targeted mutation 1, Gustav E Lienhard
MGI accession ID: MGI:2149726
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Irs4
Marker name: insulin receptor substrate 4
Chromosome: X
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.