期刊
BEHAVIOURAL BRAIN RESEARCH
卷 227, 期 1, 页码 167-174出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2011.11.002
关键词
Tubulin alpha 1; D,L-Methylphenidate; Animal model; Behavior; ENU mutagenesis; Neurodevelopmental disorder
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [21700452]
- Grants-in-Aid for Scientific Research [21220010, 21700452, 23240062, 23300161] Funding Source: KAKEN
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 Tubal 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. (C) 2011 Elsevier B.V. All rights reserved.
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