129-Iqgap1^tm1Aber/VsJ

Stock number: 025451
Product name: Iqgap1 null
Research areas: Apoptosis Research, Cardiovascular Research, Cell Biology Research, Research Tools

Description

This Iqgap1 knockout strain exhibits gastric hyperplasia, delayed differentiation of neural progenitors, increased pulmonary vascular leak and higher levels of cardiomyocyte apoptosis.

Detailed description

The Iqgap1 gene encodes a Ras GTPase-activating-like protein that acts as a cytoskeletal adaptor scaffold protein and regulates dendritic spine number and cognitive processes. These mice carry a knock out mutation of the Iqgap1 gene in which a 233 bp exon encoding amino acids 1186-1263 of the 1657 residue IQGAP1 protein is replaced by a PGK-neo cassette. Homozygotes exhibit gastric hyperplasia, delayed differentiation of neural progenitors into neuronal precursor cells, and increased pulmonary vascular leak. Prolonged cardiac pressure overload in homozygotes results in impaired cardiomyocyte hypertrophy and increased cardiomyocyte apoptosis. Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (protein) is detected by Western blot analysis of lung, liver, kidney, spleen or stomach from homozygous animals.

Development

A targeting vector designed by Dr. Andre Bernards (Massachusetts General Hospital Cancer Center and Harvard Medical School) was used to replace the 233 bp coding exon with a PGK-neo cassette in the opposite transcriptional orientation. 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 129 mice and maintained on a 129 background. Dr. Valentina A. Schmidt (Stony Brook University) obtained the mice from Dr. Andre Bernards, and continued to maintain the strain on a 129 background. 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: Iqgap1^tm1Aber
Name: targeted mutation 1, Andre Bernards
MGI accession ID: MGI:2387945
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Iqgap1
Marker name: IQ motif containing GTPase activating protein 1
Chromosome: 7
Strain of origin: 129S4/SvJae
Molecular note: The gene was disrupted by replacement of a 233 bp coding exon with a PGK-neo cassette in the reverse orientation. Complete absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis of adult and embyronic tissues using antibodies raised against the N-terminal, central, and C-terminal regions of the protein.