Sos1 Conditional Knockout mouse models

Sos1, ortholog of human SOS1, encodes the principal guanine nucleotide exchange factor for RAS, using a CDC25 homology domain and an adjacent REM domain to catalyze nucleotide release, an allosteric RAS-GTP binding site that generates positive feedback, and DH and PH domains that confer RAC exchange activity. Basal output is restrained by an amino-terminal histone fold and a carboxy-terminal proline-rich tail that binds GRB2 SH3 domains, coupling exchange to receptor tyrosine kinase phosphotyrosine. Germline gain-of-function substitutions relieve that autoinhibition and cause Noonan syndrome, so patient knockins address developmental and cardiac endpoints, while conditional nulls test the requirement for wild-type RAS loading in tumors treated with SOS1 inhibitors or with KRAS G12C inhibitors that depend on nucleotide cycling. Constitutive deletion is embryonic lethal from placental failure, whereas the paralog Sos2 supports adult viability and compensates partially, making compound Sos1 and Sos2 alleles the informative dependency design.

Conditional deletion of Sos1 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Sos1 floxed stock yields usable cohorts.