Gene disruption of medaka (Oryzias latipes) orthologue for mammalian tissue-type transglutaminase (TG2) causes movement retardation

Gene disruption of medaka (Oryzias latipes) orthologue for mammalian tissue-type transglutaminase (TG2) causes movement retardation
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哺乳动物组织型转谷氨酰胺酶 (TG2) 的青鳉 (Oryzias latipes) 直系同源基因破坏导致运动迟缓

DOI:
10.1093/jb/mvaa038
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发表时间:
2020
期刊:
The Journal of Biochemistry
影响因子:
--
通讯作者:
Hitomi Kiyotaka
Hitomi Kiyotaka
中科院分区:
--
文献类型:
--
作者:
Watanabe Yuko;Okuya Kazuho;Takada Yuki;Kinoshita Masato;Yokoi Saori;Chisada Shinichi;Kamei Yasuhiro;Tatsukawa Hideki;Yamamoto Naoyuki;Abe Hideki;Hashimoto Hisashi;Hitomi Kiyotaka

文献摘要

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转氨酶是催化蛋白质交联的酶家族,其对于若干生物功能是必需的。在以前的研究中,我们的特点是直向同源的哺乳动物转氨酶家族青鳉(Oryzias latipes),一个既定的鱼类模型。在人类同工酶中,组织型转氨酶(TG 2)具有多种功能,涉及多种生物现象。在这项研究中,我们使用CRISPR/Cas9和转录激活因子样效应物核酸酶系统建立了人类TG 2直向同源物缺陷的青鳉突变体。虽然没有观察到表型的明显形态学变化,但通过水箱潜水试验评估时发现突变鱼运动迟缓。此外,比较免疫组织化学分析在这个鱼模型中使用揭示,人TG 2的直系同源物在视顶盖的脑室周围层的表达。我们的发现为组织型转氨酶与神经系统和相关行为之间的关系提供了新的见解。
Transglutaminases are an enzyme family that catalyses protein cross-linking essential for several biological functions. In the previous studies, we characterized the orthologues of the mammalian transglutaminase family in medaka (Oryzias latipes), an established fish model. Among the human isozymes, tissue-type transglutaminase (TG2) has multiple functions that are involved in several biological phenomena. In this study, we established medaka mutants deficient for the orthologue of human TG2 using the CRISPR/Cas9 and transcription activator-like effector nucleases systems. Although apparent morphological changes in the phenotype were not observed, movement retardation was found in the mutant fish when evaluated by a tank-diving test. Furthermore, comparative immunohistochemistry analysis using in this fish model revealed that orthologue of human TG2 was expressed at the periventricular layer of the optic tectum. Our findings provide novel insight for the relationship between tissue-type transglutaminase and the nervous system and the associated behaviour.