RalGDS KO Mouse

Mouse deficient in RalGDS (a member of the RalGEF family, which control the activity of the small GTPases RalA and RalB, and also have Ras binding domains).

Contributors

Inventor Institute
Chris Marshall The Institute of Cancer Research
Cat. #: 151632
Research Fields: Cancer;Cell signaling and signal transduction;Genetics
Target: RalGDS
disease: Melanoma
Model: Knock-Out
Zygosity: Homozygous
Phenotype: RalGDS-/- mice show normal development and fertility but reduced tumour development in an established model of chemically-induced skin carcinogenesis.
Product description: The knock-out mouse was developed by Chris Marshall at the ICR and used to demonstrate a significant role for RalGDS in Ras-dependent carcinogenesis in vivo. Lack of RalGDS resulted in reduced tumour incidence, size and progression to malignancy in multistage skin carcinogenesis, and reduced transformation by Ras in tissue culture. Experiments performed in cells isolated from skin tumours suggested that RalGDS mediates cell survival through the activation of the JNK/SAPK pathway. Mouse deficient in RalGDS (a member of the RalGEF family, which control the activity of the small GTPases RalA and RalB, and also have Ras binding domains).
Conditional: No
Genetic background: Mouse RalGDS genomic clones were obtained by screening a 129/SvJ BAC library (Incyte). A targeting vector was designed using a DNA fragment extending from intron 7 to the 3'UTR, cloned into the pKO scrambler 901 vector (Stratagene). A neomycin cassette flanked by two loxP sites was cloned upstream of exon 16 and a 3rd loxP site was located in exon 8. The exons flanked by loxP sites comprise part of the catalytic domain of RalGDS and residues involved in the binding of the exchange factor to Ras. The construct was electroporated into RW4 ES cells (Incyte) and clones positive for recombination were then transiently transfected with pcrePac vector to eliminate the neomycin cassette. Cells carrying the RalGDS allele lacking exons 9-15 were injected into MF-1 blastocysts and germline-transmitting chimeric mice were obtained. Animals with a mixed MF-1/129SvJ background were used throughout. Intercrossing of RalGDS-/+ mice yielded the expected Mendelian ratios, indicating that no embryonic lethality had occurred. Moreover, RalGDS-/- male and female mice are fertile and no major defects in any organs studied have been observed.
Production details: Mouse RalGDS genomic clones were obtained by screening a 129/SvJ BAC library (Incyte). A targeting vector was designed using a DNA fragment extending from intron 7 to the 3'UTR, cloned into the pKO scrambler 901 vector (Stratagene). A neomycin cassette flanked by two loxP sites was cloned upstream of exon 16 and a 3rd loxP site was located in exon 8. The exons flanked by loxP sites comprise part of the catalytic domain of RalGDS and residues involved in the binding of the exchange factor to Ras. The construct was electroporated into RW4 ES cells (Incyte) and clones positive for recombination were then transiently transfected with pcrePac vector to eliminate the neomycin cassette. Cells carrying the RalGDS allele lacking exons 9-15 were injected into MF-1 blastocysts and germline-transmitting chimeric mice were obtained. Animals with a mixed MF-1/129SvJ background were used throughout. Intercrossing of RalGDS-/+ mice yielded the expected Mendelian ratios, indicating that no embryonic lethality had occurred. Moreover, RalGDS-/- male and female mice are fertile and no major defects in any organs studied have been observed.
Shipping conditions: Embryo/Spermatoza- Dry Ice
References:

Gonzlez-Garca et al. 2005. Cancer Cell. 7(3):219-26. PMID: 15766660.

RalGDS is required for tumor formation in a model of skin carcinogenesis.

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