PUBLICATION

Zebrafish modeling mimics developmental phenotype of patients with RAPGEF1 mutation

Authors
Li, N., Zhou, P., Yang, M., Fang, X., Krämer, N., Mughal, T.A., Abbasi, A.A., Yang, Y., Kaindl, A.M., Hu, H.
ID
ZDB-PUB-210410-8
Date
2021
Source
Clinical genetics   100(2): 144-155 (Journal)
Registered Authors
Keywords
GTPase, RAPGEF1, Zebrafish, global developmental delay
MeSH Terms
  • Humans
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Mood Disorders/genetics
  • Animals
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/blood supply
  • Female
  • Zebrafish Proteins/genetics
  • Male
  • Pedigree
  • Phenotype
  • Mutation*
  • Half-Life
  • Guanine Nucleotide-Releasing Factor 2/genetics*
  • Guanine Nucleotide-Releasing Factor 2/metabolism
  • Disease Models, Animal
  • Motor Neurons/pathology
(all 18)
PubMed
33834495 Full text @ Clin. Genet.
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.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Li, N., Zhou, P., Yang, M., Fang, X., Krämer, N., Mughal, T.A., Abbasi, A.A., Yang, Y., Kaindl, A.M., Hu, H. (2021) Zebrafish modeling mimics developmental phenotype of patients with RAPGEF1 mutation. Clinical genetics. 100(2):144-155.