A G12V mutant form of protein is conditionally expressed from the Hras1 (Harvey rat sarcoma virus oncogene 1) gene when a neomycin cassette is excised by Cre recombinase. This oncogene is involved with the development of Costello syndrome, a neuro-cardio-facio-cutaneous developmental syndrome.
Benjamin Neel, NYU School of Medicine
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), No functional change) | Hras | Harvey rat sarcoma virus oncogene |
These GV mutant mice conditionally express a mutant form of HRAS (Harvey rat sarcoma virus oncogene), which encodes a member of the Ras oncogene family involved in signal transduction pathways. Mutations in Hras are associated with Costello syndrome, a rare disorder associated with delayed development, craniofacial abnormalities, extra folds of skin, and multiple heart defects. The amino acid substitution, G12V, has the lowest GTPase activity found in codon 12 substitutions and is the predominant codon 12 mutation found in human Costello syndrome patients. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will express the mutant G12V protein in cre-expressing tissues. Mice heterozygous for the allele are viable and fertile.
The targeting vector contains a loxP-flanked neomycin cassette upstream of a modified exon 2, which contains a G12V point mutation with a unique restriction site. The mutation results in a glycine to valine change at position 12. The construct was electroporated into J1 embryonic stem (ES) cells derived from 129S4/SvJae mice. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 females and offspring were backcrossed to C57BL/6 for at least 7 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony
Allele Name | targeted mutation 1, Raju Kucherlapati |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | GV; HarasG12V |
Gene Symbol and Name | Hras, Harvey rat sarcoma virus oncogene |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 7 |
Molecular Note | The targeting vector contains a loxP-flanked neomycin cassette upstream of a modified exon 2, which contains a G12V mutation with a unique restriction site. The mutation results in a glycine to valine change at position 12. |
While maintaining a live colony, these mice are bred as heterozygotes, however, the donating investigator as not attempted to mate homozygotes.
When using the HarasG12V mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37589 in your Materials and Methods section.
Facility Barrier Level Descriptions
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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