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A hypomorphic allele reveals an important role of inturned in mouse skeletal development
Author(s) -
Chang Rachel,
Petersen Juliette R.,
Niswander Lee A.,
Liu Aimin
Publication year - 2015
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24272
Subject(s) - ciliogenesis , biology , cilium , endochondral ossification , null allele , genetics , neural tube , mutant , hedgehog , microbiology and biotechnology , embryonic stem cell , allele , gene , anatomy , embryo , cartilage
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. Developmental Dynamics 244:736–747, 2015 . © 2015 Wiley Periodicals, Inc.