This Iqgap1 knockout strain exhibits gastric hyperplasia, delayed differentiation of neural progenitors, increased pulmonary vascular leak and higher levels of cardiomyocyte apoptosis.
Valentina A Schmidt, Stony Brook University
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.
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 Name||targeted mutation 1, Andre Bernards|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Iqgap1tm1Aber; targeted mutation 1, Andre Bernards|
|Gene Symbol and Name||Iqgap1, IQ motif containing GTPase activating protein 1|
|Gene Synonym(s)||DNA segment, Chr 7, ERATO Doi 237, expressed; D7Ertd257e; p195; expressed sequence AA682088; AA682088; DNA segment, Chr 7, ERATO Doi 257, expressed; HUMORFA01; SAR1; D7Ertd237e; D7Ertd257e; mKIAA0051; D7Ertd237e|
|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.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Iqgap1 null mouse strain in a publication, please cite the originating article(s) and include JAX stock #025451 in your Materials and Methods section.
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