title: Development of an efficient screening system to identify novel bone metabolism-related genes using the exchangeable gene trap mutagenesis mouse models.
abstract: Despite numerous genetic studies on bone metabolism, understanding of the specific mechanisms is lacking. We developed an efficient screening system to identify novel genes involved in bone metabolism using mutant mouse strains registered with the Exchangeable Gene Trap Clones (EGTC) database. From 1278 trap clones in the EGTC database, 52 candidate lines were selected in the first screening, determined based on "EST profile", "X-gal", "Related article", and "Novel gene". For the second screening, bone morphometric analysis, biomechanical strength analysis, bone X-gal staining, etc. were performed on candidate lines. Forty-two male trap lines (80.8%) showed abnormalities with either bone morphometric analysis or biomechanical strength analysis. In the screening process, X-gal staining was significantly efficient (P = 0.0057). As examples, Lbr and Nedd4 trap lines selected using the screening system showed significant bone decrease and fragility, suggesting a relationship with osteoblast differentiation. This screening system using EGTC mouse lines is extremely efficient for identifying novel genes involved in bone metabolism. The gene trap lines identified as abnormal using this screening approach are highly likely to trap important genes for bone metabolism. These selected trap mice will be valuable for use as novel bio-resources in bone research.
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Syuji
authors.initials: S
authors.lastname: Kurogi
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Sekimoto
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Funamoto
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ota
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Shihoko
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Nakahara
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yoshinobu
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Japan.
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Araki
authors.affiliation: Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Japan.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Chosa
mesh_terms: D000483:Alleles; D000818:Animals; D015415:Biomarkers; D001842:Bone and Bones / Q000378:metabolism*; D030541:Databases, Genetic; D004734:Energy Metabolism / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D056726:Genetic Association Studies; D005838:Genotype; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D010641:Phenotype
chemical_list: D015415:Biomarkers