Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination
Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination
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DOI：
10.1111/gtc.12509
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发表时间：
2017-06
期刊：
影响因子：
2.1
通讯作者：
Miki Takeuchi;Chikako Inoue;Akiko Goshima;Yusuke Nagao;Koichi Shimizu;Hiroki Miyamoto;Takashi Shimizu-Takashi
中科院分区：
文献类型：
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作者：
Miki Takeuchi;Chikako Inoue;Akiko Goshima;Yusuke Nagao;Koichi Shimizu;Hiroki Miyamoto;Takashi Shimizu-Takashi
一个自发的青鳉ro突变体表现出异常的摆动和滚动游泳行为。通过定位克隆，我们将ro基因定位到含有编码接触蛋白1b（Cntn 1b）的基因的区域，接触蛋白1b是一种免疫球蛋白（IG）超家族结构域，含有膜锚定蛋白。ro突变体在cntn 1b基因中有一个缺失，引入了一个提前终止的密码子。此外，由CRISPR/Cas9系统产生的cntn 1b突变体和CRISPR突变等位基因和ro的反式杂合子具有异常的游泳行为，表明cntn 1b基因负责ro突变表型。我们还通过转录激活因子样效应核酸酶（TALENs）建立了斑马鱼cntn 1a和cntn 1b突变体。斑马鱼cntn 1b，但不cntn 1a突变体表现出异常的游泳行为类似于那些在ro突变体，这表明Cntn 1b在硬骨鱼控制游泳的神经回路的形成或功能中起着保守的作用。虽然Cntn 1缺陷小鼠有异常的小脑神经回路，但青鳉或斑马鱼cntn 1b突变体的小脑没有明显的组织学异常。青鳉cntn 1b突变体有缺陷的视动反应（OKR）适应和异常趋流性（身体定位相对于水流）。青鳉和斑马鱼cntn 1b突变体是研究运动学习和运动协调神经回路的有效模型。
A spontaneous medaka ro mutant shows abnormal wobbling and rolling swimming behaviors. By positional cloning, we mapped the ro locus to a region containing the gene encoding Contactin1b (Cntn1b), which is an immunoglobulin (Ig)‐superfamily domain‐containing membrane‐anchored protein. The ro mutant had a deletion in the cntn1b gene that introduced a premature stop codon. Furthermore, cntn1b mutants generated by the CRISPR/Cas9 system and trans‐heterozygotes of the CRISPR mutant allele and ro had abnormal swimming behavior, indicating that the cntn1b gene was responsible for the ro‐mutant phenotype. We also established zebrafish cntn1a and cntn1b mutants by transcription activator‐like effector nucleases (TALENs). Zebrafish cntn1b but not cntn1a mutants showed abnormal swimming behaviors similar to those in the ro mutant, suggesting that Cntn1b plays a conserved role in the formation or function of the neural circuits that control swimming in teleosts. Although Cntn1‐deficient mice have abnormal cerebellar neural circuitry, there was no apparent histological abnormality in the cerebellum of medaka or zebrafish cntn1b mutants. The medaka cntn1b mutants had defective optokinetic response (OKR) adaptation and abnormal rheotaxis (body positioning relative to water flow). Medaka and zebrafish cntn1b mutants are effective models for studying the neural circuits involved in motor learning and motor coordination.