Irie Masahito, Yoshikawa Masanobu, Ono Ryuichi, Iwafune Hirotaka, Furuse Tamio, Yamada Ikuko, Wakana Shigeharu, Yamashita Yui, Abe Takaya, Ishino Fumitoshi, Kaneko-Ishino Tomoko
School of Health Sciences, Tokai University, Isehara, Kanagawa, Japan; Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.
Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
PLoS Genet. 2015 Sep 24;11(9):e1005521. doi: 10.1371/journal.pgen.1005521. eCollection 2015 Sep.
Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.
小鼠寿司一相关逆转录转座子同源物11/含锌指CCHC结构域16（Sirh11/Zcchc16）的基因靶向导致与认知相关的异常行为，包括注意力、冲动性和工作记忆。Sirh11/Zcchc16编码一种CCHC型锌指蛋白，该蛋白与LTR逆转录转座子Gag蛋白具有高度同源性。在对前额叶皮质区域进行微透析分析时，在基因敲除（KO）小鼠中灌注含高钾的人工脑脊液后，去甲肾上腺素（NA）的回收率与多巴胺（DA）相比有所降低。这些数据表明，在当代小鼠发育系统中，Sirh11/Zcchc16可能通过去甲肾上腺素能系统参与大脑的认知功能。有趣的是，它在真兽类的四个主要类群中的三个类群，即灵长总目、劳亚兽总目和非洲兽总目中高度保守，但在树懒和犰狳等异关节类物种中发生了严重突变，这表明它在包括人类和小鼠在内的三个主要真兽类谱系的大脑进化中发挥了作用。Sirh11/Zcchc16是第一个参与大脑功能的SIRH基因，而不像Peg10、Peg11/Rtl1和Sirh7/Ldoc1那样仅参与胎盘功能。
