title: An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda.
abstract: The mechanisms that regulate bone mass are important in a variety of complex diseases such as osteopenia and osteoporosis. Regulation of bone mass is a polygenic trait and is also influenced by various environmental and lifestyle factors, making analysis of the genetic basis difficult. As an effort toward identifying novel genes involved in regulation of bone mass, N-ethyl-N-nitrosourea (ENU) mutagenesis in mice has been utilized. Here we describe a mouse mutant termed Yoda that was identified in an ENU mutagenesis screen for dominantly acting mutations. Mice heterozygous for the Yoda mutation exhibit craniofacial abnormalities: shortened snouts, wider skulls, and deformed nasal bones, underlined by altered morphology of frontonasal sutures and failure of interfrontal suture to close. A major feature of the mutant is reduced bone mineral density. Homozygosity for the mutation results in embryonic lethality. Positional cloning of the locus identified a missense mutation in a highly conserved region of the ankyrin repeat domain 11 gene (Ankrd11). This gene has not been previously associated with bone metabolism and, thus, identifies a novel genetic regulator of bone homeostasis.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell. I.Barbaric@sheffield.ac.uk
authors.forename: Ivana
authors.initials: I
authors.lastname: Barbaric
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Perry
authors.forename: T Neil
authors.initials: TN
authors.lastname: Dear
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rodrigues Da Costa
authors.forename: Daniela
authors.initials: D
authors.lastname: Salopek
authors.forename: Ana
authors.initials: A
authors.lastname: Marusic
authors.forename: Tertius
authors.initials: T
authors.lastname: Hough
authors.forename: Sara
authors.initials: S
authors.lastname: Wells
authors.forename: A Jackie
authors.initials: AJ
authors.lastname: Hunter
authors.forename: Michael
authors.initials: M
authors.lastname: Cheeseman
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015519:Bone Density / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000235:genetics*; D017124:Conserved Sequence; D019465:Craniofacial Abnormalities / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005038:Ethylnitrosourea; D005260:Female; D005804:Genes, Lethal; D007738:Kyphosis / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains / Q000196:embryology / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D012097:Repressor Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C528115:Ankrd11 protein, mouse; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D005038:Ethylnitrosourea