Raf1 Conditional Knockout mouse models

Encoding CRAF, Raf1 is the mouse ortholog of human RAF1 and produces a serine and threonine kinase held autoinhibited by 14-3-3 binding at phospho-Ser259 and by its cysteine-rich domain until RAS-GTP engages the RAS-binding domain at the membrane, after which SHOC2 and PP1 dephosphorylation, Ser338 phosphorylation and side-to-side dimerization with BRAF generate an active kinase that phosphorylates MEK1 and MEK2. Germline Noonan syndrome substitutions such as S257L and S259F disrupt the 14-3-3 brake and cause hypertrophic cardiomyopathy, providing a knockin design distinct from a null, and kinase-independent functions in ASK1 and ROK alpha regulation argue for kinase-dead knockins alongside deletion. Constitutive deletion is embryonic lethal with widespread apoptosis on most backgrounds, so conditional nulls are needed for adult work. Araf and Braf occupy the same dimer interface and partially compensate, so interpret single-locus loss against dimerization-competent paralog expression in the target tissue.

Conditional deletion of Raf1 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 Raf1 floxed stock yields usable cohorts.