title: Behavioral and neuromorphological characterization of a novel Tuba1 mutant mouse.
abstract: As part of the RIKEN large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis project, we screened mice with a dominant mutation that exhibited abnormal behavior using an open-field test and a home-cage activity test. We tested 495 male progeny of C57BL/6J males treated with ENU and untreated C3H/HeJ females using the open-field test and isolated behavioral mutant M101736, which exhibited a significant increase in spontaneous locomotor activity. We identified a missense mutation in the Tuba1 gene, which encodes the TUBA1 protein, and designated the mutant gene Tuba1(Rgsc1736). This mutation results in an aspartic acid to glycine substitution in the TUBA1 protein. Detailed analyses revealed that Tuba1(Rgsc1736) heterozygotes exhibited inattention to novel objects and aberrant patterns of home-cage activity. The results of a behavioral pharmacological analysis using methylphenidate and morphological analyses of embryonic and adult brains suggested that Tuba1(Rgsc1736) is a novel animal model for neurodevelopmental disorders.
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN Bioresource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Furuse
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kushida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masuya
authors.forename: Ikuo
authors.initials: I
authors.lastname: Miura
authors.forename: Hideki
authors.initials: H
authors.lastname: Kaneda
authors.forename: Kimio
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Wada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yuasa
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000235:genetics; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D001973:Bromodeoxyuridine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D003623:Dark Adaptation / Q000187:drug effects / Q000235:genetics; D002658:Developmental Disabilities / Q000188:drug therapy / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005038:Ethylnitrosourea / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006702:Homing Behavior / Q000502:physiology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics* / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D016296:Mutagenesis / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology; D019579:Neocortex / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D010641:Phenotype; D013997:Time Factors; D014404:Tubulin / Q000235:genetics*
chemical_list: D000697:Central Nervous System Stimulants; D009153:Mutagens; C569741:Tuba1a protein, mouse; D014404:Tubulin; D008774:Methylphenidate; D001224:Aspartic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D001973:Bromodeoxyuridine; D005038:Ethylnitrosourea; D005998:Glycine