An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda.
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.
Barbaric
Ivana
I
MRC Mammalian Genetics Unit, Harwell. I.Barbaric@sheffield.ac.uk
Perry
Mark J
MJ
Dear
T Neil
TN
Rodrigues Da Costa
Alexandra
A
Salopek
Daniela
D
Marusic
Ana
A
Hough
Tertius
T
Wells
Sara
S
Hunter
A Jackie
AJ
Cheeseman
Michael
M
Brown
Steve D M
SD
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
C528115:Ankrd11 protein, mouse; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D005038:Ethylnitrosourea