Smo Conditional Knockout mouse models

Smo, the ortholog of human SMO, encodes a class F G protein coupled receptor with a seven-transmembrane bundle plus an extracellular cysteine-rich domain that binds cholesterol, the activating sterol whose access is restricted by PTCH1 until Hedgehog engagement. Activation drives SMO accumulation in the primary cilium, phosphorylation by GRK2 and CK1, suppression of PKA-dependent GLI3 processing and release of GLI2 activator. Oncogenic substitutions such as the SmoM2 allele and the vismodegib resistance mutation D473H make Cre-inducible knockins, particularly the lox-stop-lox SmoM2 allele, the standard tools for driving pathway activation in a defined lineage and for modeling acquired inhibitor resistance. Germline deletion is embryonic lethal with cardiac and left to right asymmetry defects, so conditional nulls are required to test ligand dependence in adult tissues. Match allele class to question: activating knockin for tumor initiation and drug resistance, conditional null for pathway requirement and ciliary trafficking.

Tissue restricted knockout of Smo keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.