Behavioral and neuromorphological characterization of a novel Tuba1 mutant mouse
Behavioral and neuromorphological characterization of a novel Tuba1 mutant mouse
复制标题
DOI：
10.1016/j.bbr.2011.11.002
复制
发表时间：
2012-02-01
影响因子：
2.7
通讯作者：
Wakana, Shigeharu
中科院分区：
文献类型：
--
作者：
Furuse, Tamio;Yamada, Ikuko;Wakana, Shigeharu
作为RIKEN大规模N-乙基-N-亚硝基脲（ENU）诱变项目的一部分，我们使用旷场试验和笼内活动试验筛选了具有显性突变的表现出异常行为的小鼠。我们测试了495名男性后代的C57 BL/6 J男性与ENU和未处理的C3 H/HeJ女性使用开放领域的测试和分离的行为突变体M101736，表现出自发运动活动的显着增加。我们在Tubal基因中发现了一个错义突变，该基因编码TUBA 1蛋白，并命名为突变基因Tuba 1（Rgsc 1736）。该突变导致TUBA 1蛋白中天冬氨酸被甘氨酸取代。详细的分析表明，Tuba 1（Rgsc 1736）杂合子表现出不注意新的对象和异常模式的家庭笼活动。使用哌甲酯的行为药理学分析和胚胎和成人大脑的形态学分析的结果表明，Tuba 1（Rgsc 1736）是一种新的神经发育障碍的动物模型。(C)2011 Elsevier B. V.保留所有权利。
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.