title: A hypomorphic allele reveals an important role of inturned in mouse skeletal development.
abstract: 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.
authors.affiliation: Department of Biology, Eberly College of Science, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Rachel
authors.initials: R
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Juliette R
authors.initials: JR
authors.lastname: Petersen
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Niswander
authors.affiliation: Department of Biology, Eberly College of Science, The Pennsylvania State University, University Park, Pennsylvania.|Center for Cellular Dynamics, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Aimin
authors.initials: A
authors.lastname: Liu
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000196:embryology; D016764:Cell Polarity; D002478:Cells, Cultured; D002923:Cilia / Q000648:ultrastructure; D006130:Growth Disorders / Q000235:genetics; D053823:Hedgehog Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009436:Neural Tube Defects / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics*; D000072079:Patched Receptors; D017354:Point Mutation; D017689:Polydactyly / Q000196:embryology / Q000235:genetics; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; C568405:inturned protein, mouse
keywords: Hedgehog signaling; ciliogenesis; endochondral ossification; polydactyly; primary cilia; skeletal development