Shh Conditional Knockout mouse models

Shh is the mouse ortholog of human SHH and encodes Sonic hedgehog, which autoprocesses to attach cholesterol to the carboxy terminus of its signaling fragment and receives palmitate at Cys24 from HHAT, then depends on DISP1 and SCUBE2 for release before binding PTCH1 with the coreceptors CDON, BOC, and GAS1 to relieve SMO inhibition and shift ciliary GLI processing from GLI3 repressor toward activator forms. It patterns the ventral neural tube as floor plate signal and specifies digit identity from the zone of polarizing activity, and human mutations cause holoprosencephaly type 3 while pathway-activating PTCH1 and SMO lesions drive basal cell carcinoma and medulloblastoma. Nulls die with cyclopia and severe midline defects, so conditional deletion, holoprosencephaly missense knockins, and ZRS limb enhancer alleles each answer distinct questions. Ihh and Dhh overlap in gut and gonad, and Shh-Cre lines double as lineage drivers worth validating before use.

A floxed Shh allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.