loading page

Zebrafish modeling mimics developmental phenotype of patients with RAPGEF1 mutation
  • +6
  • Na Li,
  • Pei Zhou,
  • Miaomiao Yang,
  • Xiang Fang,
  • Nadine Krämer,
  • Tauqeer Ahmed Mughal,
  • Ansar Abbassi,
  • Angela Kaindl,
  • Hao Hu
Na Li
Guangzhou Women and Children's Medical Center

Corresponding Author:[email protected]

Author Profile
Pei Zhou
Guangzhou Women and Children's Medical Center
Author Profile
Miaomiao Yang
Guangzhou Women and Children's Medical Center
Author Profile
Xiang Fang
Guangzhou Women and Children's Medical Center
Author Profile
Nadine Krämer
Charité Universitätsmedizin Berlin
Author Profile
Tauqeer Ahmed Mughal
Mirpur University of Science and Technology
Author Profile
Ansar Abbassi
Department of Zoology
Author Profile
Angela Kaindl
Charité Universitätsmedizin Berlin
Author Profile
Hao Hu
Guangzhou Women and Children's Medical Center
Author Profile

Abstract

RAPGEF1 is a guanine nucleotide exchange factor responsible for transmitting extracellular signals to the Ras family of GTPase located at the inside of membrane. Here, we report for the first time a homozygous mutation of RAPGEF1 in a consanguineous family with two siblings affected by neuropsychiatric disorder. To confirm the correlation of the mutation and the phenotype, we utilized in silico analysis and established a zebrafish model. Survival rate was reduced in the rapgef1a-knockdown model, and the zebrafish showed global morphological abnormalities, particularly of brain and blood vessels. Co-application of human RAPGEF1 wildtype mRNA effectively rescued the abnormal phenotype, while that of RAPGEF1 mRNA carrying the human mutation did not. This work is the first report of a human Mendelian disease associated with RAPGEF1 and the first report of a zebrafish model built for this gene. The phenotype of zebrafish model provides further evidence that defective RAPGEF1 may lead to global developmental delay in human patients.