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

Transglutaminases (TGases) are an enzyme family that catalyzes protein cross-linking essential for several biological functions. In the previous studies, we characterized the orthologues of the mammalian TGase 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 (OlTGT) using the CRISPR/Cas9 and TALEN 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 OlTGT was expressed at the periventricular layer of the optic tectum. Our findings provide novel insight for the relationship between tissue-type TGase and the nervous system and the associated behavior.