Grlf1 (glucocorticoid receptor DNA binding factor 1) encodes p190 RhoGAP, a member of the Rho family of small GTPases which are critical regulators of actin cytoskeleton organization. p190 RhoGAP is expressed throughout the developing nervous system where it is involved in hippocampal dendritic spine and synapse stability. In this strain a neo cassette replaces part of exon 1, containing the translation initiation site and the GTPase domain, thereby abolishing gene function. Heterozygotes are viable and fertile. Homozygotes are not viable and have abnormalities in fusing the forebrain hemispheres, neural tube closure, forming the optic cup, shaping ventricles, and layering of the cerebral cortex.
A targeting vector was designed to replace part of exon 1, including the translation initiation site, of the glucocorticoid receptor DNA binding factor 1 (Grlf1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric mice were bred to C57BL/6J mice. These mice were maintained on a mixed C57BL/6J;129S2 background. Once these mice arrived in Dr. Koleske's lab at Yale University they were bred to mice on a mixed C57BL/6J;129SvJ background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Jeffrey Settleman|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Arhgap35-; RhoGAP-; p190 RhoGAP-; p190-; p190rhogap-|
|Gene Symbol and Name||Arhgap35, Rho GTPase activating protein 35|
|Gene Synonym(s)||6430596G11Rik; 6430596G11Rik; AI841135; GRF-1; GRLF1; Grlf1; Grlf1; P190 RhoGAP; P190-A; P190A; RIKEN cDNA 6430596G11 gene; expressed sequence AI841135; glucocorticoid receptor DNA binding factor 1; p190A; p190ARhoGAP; p190RhoGAP|
|Strain of Origin||129S2/SvPas|
|Molecular Note||1.5 kb of sequence, including the start codon and encoding the GTPase domain, was replaced by a PGK-neo cassette. While normal protein was undetected by Western blot analysis of homozygous mutant embryo brain lysates, an aberrant protein generated from an internal start codon was identified at a level similar to that of the wild-type protein. Though sequence encoding the RasGAP binding and RhoGAP domains was retained by the mutant allele, the mutant protein failed to undergo tyrosine phosphorylation or RasGAP association in the brain. Analysis of heterozygous mice indicated improper localization of the mutant protein. Whereas 34% of the wild-type protein was isolated in a detergent-insoluble fraction of brain lysate, only 7% of the mutant protein was present in the same fraction. In addition, study of MEFs indicated differential subcellular localization.|
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or B6129SF1/J mice (Stock No. 101043). Homozygotes are not viable.
When using the B6;129-Arhgap35tm1Jset/AjkJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #020997 in your Materials and Methods section.
|Heterozygous or wildtype forGrlf1<tm1Jset>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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