Objective To determine if ARHGEF10 has a haploinsufficient effect and provide evidence to evaluate the severity, if any, during prenatal consultation. Methods Zebrafish was used as a model for generating mutant. The pattern of arhgef10 expression in the early stages of zebrafish development was observed using whole-mount in situ hybridization (WISH). CRISPR/Cas9 was applied to generate a zebrafish model with a single-copy or homozygous arhgef10 deletion. Activity and light/dark tests were performed in arhgef10?/?, arhgef10+/?, and wild-type zebrafish larvae. ARHGEF10 was knocked down using small interferon RNA (siRNA) in the SH-SY5Y cell line, and cell proliferation and apoptosis were determined using the CCK-8 assay and Annexin V/PI staining, respectively. Results WISH showed that during zebrafish embryonic development arhgef10 was expressed in the midbrain and hindbrain at 36–72 h post-fertilization (hpf) and in the hemopoietic system at 36–48 hpf. The zebrafish larvae with single-copy and homozygous arhgef10 deletions had lower exercise capacity and poorer responses to environmental changes compared to wild-type zebrafish larvae. Moreover, arhgef10?/? zebrafish had more severe symptoms than arhgef10+/- zebrafish. Knockdown of ARHGEF10 in human neuroblastoma cells led to decreased cell proliferation and increased cell apoptosis.Conclusion Based on our findings, ARHGEF10 appeared to have a haploinsufficiency effect.

ZHANG Yi;AN Ming Xing;GONG Chen;LI Yang Yang;WANG Yu Tong;LIN Meng;LI Rong;TIAN Chan

Department of Obstetrics and Gynecology,Center for Medical Genetics,School of Basic Medical Sciences,Third Hospital,Peking University,Beijing 100191,China;Key Laboratory of Assisted Reproduction(Peking University),Ministry of Education,Beijing 100191,China;Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology,Beijing 100191,China;National Clinical Research Center for Obstetrics and Gynecology,Beijing 100191,China;Department of Medical Genetics,Center for Medical Genetics,Peking University Health Science Center,Beijing 100191,China

生物医学与环境科学（英文版）

[1]ZHANG Yi;AN Ming Xing;GONG Chen;LI Yang Yang;WANG Yu Tong;LIN Meng;LI Rong;TIAN Chan-.Single-copy Loss of Rho Guanine Nucleotide Exchange Factor 10 (arhgef10) Causes Locomotor Abnormalities in Zebrafish Larvae)[J].生物医学与环境科学（英文版）,2022(01):35-44

arhgef10,ARHGEF10,haploinsufficient,arhgef10+,hindbrain,hemopoietic,haploinsufficiency

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