C57BL/6-Rac1^tm1Jdo/J

Stock number: 033790
Product name: Rac1^LSL-P29S
Research areas: Cancer Research, Research Tools

Description

Rac1^LSL-P29S mice carry a point mutation (P29S) in exon 2 of the Rac1 gene, expression of which is blocked by the presence of a loxP-flanked STOP cassette. This strain may be useful when studying melanoma development.

Detailed description

The Rac1^LSL-P29S allele has a loxP-flanked STOP cassette upstream of exon 2 of the Rac family small GTPase 1 (Rac1) gene. Exon 2 was modified to harbor a missense mutation at codon 29, resulting in a proline to serine mutation (P29S) commonly found in patients with cutaneous melanoma. RAC1 encodes a RHO family small GTPase involved in cellular processes including growth, differentiation, movement and lipid vesicle transport. This amino acid change arises from a UV radiation-induced C to T transition at a dipyrimidine site.

Homozygous Rac1^LSL-P29S mice are embryonic lethal, while some lethality is also observed among heterozygous mice (34-38% produced vs. 50% expected). The STOP cassette prevents the expression of mutant RAC1 until it is removed by Cre-mediated recombination of the loxP sites, thus allowing expression of RAC1.

Widespread expression of RAC1^P29S at endogenous levels in adult mice promotes gradual development of B cell lymphoma, while being developmentally lethal when expressed in the embryo. RAC1^P29S also promotes the progression of melanocytic hyperplasia to melanoma when expressed in melanocytes in combination with other genetic aberrations commonly found in melanoma (BRAF^V600E or NF1-loss).

Development

The Rac1^LSL-P29S targeting vector was designed to insert a loxP-flanked STOP cassette, containing a hygromycin resistance cassette upstream of exon 2 of the Rac family small GTPase 1 (Rac1) gene. Exon 2 was modified to harbor a missense mutation at codon 29, resulting in a proline to serine mutation (P29S) commonly found in patients with cutaneous melanoma. The construct was electroporated into C57BL/6NTac-derived PRX-B6N embryonic stem (ES) cells. ES cells were injected into blastocysts and resulting chimeric males were mated to C57BL/6J females. Resulting Rac1^LSL-P29S mice were bred to C57BL/6J mice for at least 10 generations. Upon arrival at The Jackson Laboratory Repository, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Rac1^tm1Jdo
Name: targeted mutation 1, Julian Downward
MGI accession ID: MGI:6314340
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Humanized sequence
Synonyms: Rac1^LSL-P29S
Marker symbol: Rac1
Marker name: Rac family small GTPase 1
Marker synonyms: D5Ertd559e; MIG5; MRD48; p21-Rac1; Rac-1; TC-25
Chromosome: 5
Strain of origin: C57BL/6NTac
Molecular note: The targeting vector is designed to insert a loxP-flanked STOP cassette, containing a neomycin resistance cassette, upstream of exon 2 of the gene. Exon 2 was modified to harbor a missense mutation at codon 29, resulting in a proline to serine mutation (P29S) commonly found in patients with cutaneous melanoma.