Background: Cilia are important for Hedgehog signaling in vertebrates and many genes that encode proteins involved in ciliogenesis have been studied for their roles in embryonic development. Null mutations in many of these genes cause early embryonic lethality, hence an understanding of their roles in postnatal development is limited.
Results: The Inturned (Intu) gene is required for ciliogenesis and here we report a recessive hypomorphic mutation, resulting in substitution of a conserved hydrophobic residue (I813N) near the C-terminus, that sheds light on later functions of Intu. Mice homozygous for this Double-thumb (Intu(Dtm)) allele exhibit polydactyly, retarded growth, and reduced survival. There is a moderate loss of cilia in Intu(Dtm/Dtm) mutants, and Intu(I813N) exhibits compromised ability to increase ciliogenesis in cultured Intu null mutant cells. Intu(Dtm) mutants show rib defects and delay of endochondral ossification in long bones, digits, vertebrae, and the sternum. These skeletal defects correlate with a decrease in Hh signaling. However, patterning of the neural tube and planar cell polarity appear to be normal.
Conclusions: This hypomorphic Intu allele highlights an important role of Intu in mouse skeletal development.
Keywords: Hedgehog signaling; ciliogenesis; endochondral ossification; polydactyly; primary cilia; skeletal development.
© 2015 Wiley Periodicals, Inc.