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
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|
|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|
|Strain of Origin||129S4/SvJae|
|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.