Ihh Knockout mouse models

Ihh, the mouse ortholog of human IHH, encodes Indian hedgehog, a lipid-modified morphogen that undergoes autocatalytic cleavage with cholesterol addition to its signaling fragment and palmitoylation by HHAT before release, then binds PTCH1 to relieve inhibition of SMO and shift ciliary GLI processing from repressor toward activator forms. Prehypertrophic chondrocytes secrete it to induce PTHrP in periarticular cells, and that negative feedback circuit sets the pace of chondrocyte proliferation and the position of the hypertrophic zone, while perichondrial signaling specifies osteoblast progenitors during endochondral ossification. Nulls show severe dwarfism with disorganized growth plates and die around birth, so conditional deletion with Col2a1-Cre or Prx1-Cre is required for postnatal skeletal work. Brachydactyly type A1 missense knockins model altered ligand range rather than absence, and humanization aids pathway inhibitor testing. Shh and Dhh overlap in gut and gonad, so compound alleles matter outside the skeleton.

Whole body loss of Ihh gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.