Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish.
Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish.
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DOI：
10.3390/ijms23158389
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发表时间：
2022-07-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
在几个队列中，KATNAL2突变与自闭症谱系障碍（ASD）和其他相关的神经发育障碍（ndd）如智力残疾（ID）有关。KATNAL2与大脑发育有关，因为它是爪蟾纤毛形成和小鼠树突生长所必需的。然而，Katnal2功能破坏与行为缺陷之间的因果关系尚未建立。在这里，我们使用CRISPR/ cas9介导的基因组编辑在斑马鱼中生成了一个katnal2零等位基因，并进行了形态和行为表征。我们观察到katnal2-/-胚胎发育延迟，特别是在收敛和伸展（CE）运动中。孵化出的幼虫显示出较小的大脑大小和体长。在行为测试中，katnal2-/-斑马鱼在幼虫和成鱼中都表现出运动活动的减少；幼虫夜间清醒活动增加；成年人的焦虑行为增强，社会互动受损，社会凝聚力降低。这些发现表明katnal2在发育和行为中发挥重要作用，为研究与katnal2突变相关的ASD机制提供了体内模型。
KATNAL2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders (NDDs) such as intellectual disability (ID) in several cohorts. KATNAL2 has been implicated in brain development, as it is required for ciliogenesis in Xenopus and is required for dendritic arborization in mice. However, a causative relationship between the disruption of Katnal2 function and behavioral defects has not been established. Here, we generated a katnal2 null allele in zebrafish using CRISPR/Cas9-mediated genome editing and carried out morphological and behavioral characterizations. We observed that katnal2-/- embryos displayed delayed embryonic development especially during the convergence and extension (CE) movement. The hatched larvae showed reduced brain size and body length. In the behavioral tests, the katnal2-/- zebrafish exhibited reduced locomotor activity both in larvae and adults; increased nocturnal waking activity in larvae; and enhanced anxiety-like behavior, impaired social interaction, and reduced social cohesion in adults. These findings indicate an important role for katnal2 in development and behavior, providing an in vivo model to study the mechanisms underlying the ASD related to KATNAL2 mutations.
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影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
3.5
作者：
Koh, Angela;Tao, Shijie;Winkler, Christoph
通讯作者：
Winkler, Christoph
影响因子：
13.8
作者：
Kalueff, Allan V.;Stewart, Adam Michael;Gerlai, Robert
通讯作者：
Gerlai, Robert
自闭症谱系障碍。
DOI：
10.1038/s41572-019-0138-4
发表时间：
2020-01-16
期刊：
Nature reviews. Disease primers
影响因子：
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作者：
Lord C;Brugha TS;Charman T;Cusack J;Dumas G;Frazier T;Jones EJH;Jones RM;Pickles A;State MW;Taylor JL;Veenstra-VanderWeele J
通讯作者：
Veenstra-VanderWeele J
影响因子：
46.9
作者：
通讯作者：
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