129S-Iqgap2^tm1Vs/J

Stock number: 025452
Product name: Iqgap2 null
Research areas: Cancer Research, Metabolism Research, Research Tools

Description

This Iqgap2 knockout strain is useful in studies of apoptosis, hepatocellular carcinoma and metabolic homeostasis.

Detailed description

The Iqgap2 gene encodes a Ras GTPase-activating-like scaffold protein, which is interacts with the cytoskeleton, cell adhesion molecules and signaling molecules. These mice carry a knock out mutation of the Iqgap2 gene, in which a PGK-NEO cassette was used to disrupt a 36,241 bp genomic fragment which included exons 18 to 30. The mutation results in loss of part of the IQ2 and all of the IQ3, IQ4, and RasGAP-related domain motifs. Mice that are homozygous for the targeted mutation are viable and fertile. QRT-PCR confirmed the absence of transcript in hepatocytes and immunoblot analysis confirmed the absence of protein in liver, spleen, heart, and kidney lysates. Homozygotes develop spontaneous hepatocellular carcinoma by the age of 18-24 months. Facilitated long-chain fatty acids (LCFA) uptake is impaired, which protects from high fat diet-induced hepatic steatosis and insulin resistance. The lifespan of the null mice is shorter compared to wildtype littermates.

Development

A targeting vector containing a PGK-NEO cassette was used to disrupt a 36,241 bp genomic fragment which included exons 18 to 30. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were introduced into C57BL/6 blastocysts. The resulting chimeric animals were bred with 129S4/SvJae mice, and then backcrossed to 129S4/SvJae for 8 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.

Allele

Symbol: Iqgap2^tm1Vs
Name: targeted mutation 1, Valentina A Schmidt
MGI accession ID: MGI:3526416
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Iqgap2
Marker name: IQ motif containing GTPase activating protein 2
Chromosome: 13
Strain of origin: 129S4/SvJae
Molecular note: A 36,241 bp genomic fragment spanning exons 18 - 31 was replaced with a PGK-neo cassette via homologous recombination. This resulted in removal of part of the IQ2 and all of the IQ3, IQ4, and GRD motifs. QRT-PCR confirmed the absence of transcript in hepatocytes and immunoblot analysis confirmed the absence of protein in liver, spleen, heart, and kidney lysates. Only in the liver was a modest increase in Iqgap1 expression detected. QRT-PCR analysis did not detect any change in F2rl2 (coding sequence contained within intron 13 of Iqgap2) expression.