B6;129-Irs2^tm1Mfw/J

Stock number: 004421
Product name: IRS-2 KO
Research areas: Diabetes and Obesity Research

Description

These Irs2 knock-out mice exhibit a progressive development of a type 2 diabetic phenotype.

Detailed description

Mice homozygous for the targeted allele are viable yet sterile and exhibit a progressive development of a type 2 diabetic phenotype. At birth, mice are slightly (10%) smaller than wildtype littermates. This weight difference is maintained from birth through adulthood. Elevated blood sugar levels can be detected by 3 days of age. By 3-6 weeks of age mice develop fasting hyperglycemia and become diabetic by 10 weeks. A reduced beta-cell mass can be detected by 4 weeks and a profound insulin resistance is observed in skeletal muscle and liver tissue by 6-8 weeks. Levels of fasting sugars continue to rise until male mice eventually succumb to dehydration and hyperosomolar coma. Female mice, while exhibiting a similar progression, tend not to die. This mutant mouse represents a model useful in studies related to type 2 diabetes.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to delete the entire insulin receptor 2 gene. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells in the laboratory of Dr. Morris White, Joslin Diabetes Center/HHMI, Boston. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice.

Allele

Symbol: Irs2^tm1Mfw
Name: targeted mutation 1, Morris F White
MGI accession ID: MGI:2158686
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Irs2
Marker name: insulin receptor substrate 2
Chromosome: 8
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A targeting vector containing a PGK-neomycin cassette replaced the entire gene. Lack of protein was demonstrated in liver and muscle extracts by Western analysis in homozygous mutant animals.