Thm2 interacts with paralog, Thm1, and sensitizes to Hedgehog signaling in postnatal skeletogenesis.

ABSTRACT: Mutations in the intraflagellar transport-A (IFT-A) gene, THM1, have been identified in skeletal ciliopathies. Here, we report a genetic interaction between Thm1, and its paralog, Thm2, in postnatal skeletogenesis. THM2 localizes to primary cilia, but Thm2 deficiency does not affect ciliogenesis and Thm2-null mice survive into adulthood. However, by postnatal day 14, Thm2^-/-; Thm1^aln/+ mice exhibit small stature and small mandible. Radiography and microcomputed tomography reveal Thm2^-/-; Thm1^aln/+ tibia are less opaque and have reduced cortical and trabecular bone mineral density. In the mutant tibial growth plate, the proliferation zone is expanded and the hypertrophic zone is diminished, indicating impaired chondrocyte differentiation. Addition

SUBMITTER: Allard BA 

PROVIDER: S-EPMC9278483 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature