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Gene disruption of medaka (Oryzias latipes) orthologue for mammalian tissue-type transglutaminase (TG2) causes movement retardation.
The Journal of Biochemistry ( IF 2.7 ) Pub Date : 2020-06-24 , DOI: 10.1093/jb/mvaa038
Yuko Watanabe 1 , Kazuho Okuya 1 , Yuki Takada 1 , Masato Kinoshita 2 , Saori Yokoi 3 , Shinichi Chisada 4 , Yasuhiro Kamei 5 , Hideki Tatsukawa 1 , Naoyuki Yamamoto 6 , Hideki Abe 6 , Hisashi Hashimoto 7 , Kiyotaka Hitomi 1
Affiliation  

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.

中文翻译:

哺乳动物组织型转谷氨酰胺酶(TG2)的高加索(Oryzias latipes)直向同源物的基因破坏导致运动延迟。

转谷氨酰胺酶是一个酶家族,催化几种生物学功能必不可少的蛋白质交联。在以前的研究中,我们对medaka(Oryzias latipes)哺乳动物转谷氨酰胺酶家族的直向同源物进行了鉴定。),建立了鱼模型。在人类同工酶中,组织型转谷氨酰胺酶(TG2)具有涉及多种生物学现象的多种功能。在这项研究中,我们使用CRISPR / Cas9和转录激活因子样效应核酸酶系统建立了缺乏人TG2直向同源基因的medaka突变体。尽管未观察到表型的明显形态变化,但通过储罐潜水试验进行评估时,在突变鱼类中发现了运动迟缓。此外,在该鱼模型中使用的比较免疫组织化学分析显示,人TG2的直向同源物在视神经支架的脑室周围层表达。我们的发现为组织型转谷氨酰胺酶与神经系统和相关行为之间的关系提供了新颖的见解。
更新日期:2020-06-24
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