ZFIN ID: ZDB-PUB-180929-2
Loss of Leucyl-tRNA synthetase b leads to ILFS1-like symptoms in zebrafish
Wang, Z., Song, J., Luo, L., Ma, J.
Date: 2018
Source: Biochemical and Biophysical Research Communications   505(2): 378-384 (Journal)
Registered Authors: Luo, Lingfei
Keywords: ILFS1, Leucyl-tRNA synthetase b, Liver, Zebrafish, mTORC1
MeSH Terms:
  • Amino Acyl-tRNA Synthetases/deficiency*
  • Amino Acyl-tRNA Synthetases/genetics
  • Animals
  • Cell Proliferation
  • DNA Damage
  • Liver Failure/drug therapy
  • Liver Failure/enzymology*
  • Liver Failure/genetics
  • Liver Failure/pathology
  • Mutant Proteins
  • Mutation
  • Signal Transduction
  • Sirolimus/therapeutic use
  • Transcription Factors/physiology
  • Zebrafish
  • Zebrafish Proteins/physiology
PubMed: 30262142 Full text @ Biochem. Biophys. Res. Commun.
Leucyl-tRNA synthetase (LARS) is a kind of aminoacyl-tRNA synthetases (aaRSs), which is important for protein synthesis. Following the discovery of three clinical cases which carry LARS mutations, it has been designated as the infantile liver failure syndrome type 1 (ILFS1) gene. ILFS1 is a kind of infantile hepatopathy, which is difficult to diagnose and manage. As the mechanism underlying this disease is poorly understood and LARS is conserved among vertebrates, we obtained zebrafish larsbcq68 mutant via CRISPR/Cas9 technology to investigate the role of larsb in vivo. In mutant, the proliferation ability of liver was drastically decreased at later stages accompanied with severe DNA damage. Further studies demonstrated that the mTORC1 signaling was hyperactivated in larsbcq68 mutant. Inhibition of mTORC1 signaling pathway by Rapamycin or mTORC1 morpholino can partially rescue the liver failure of the mutants. These data revealed that larsb mutation caused ILFS1-like phenotype in zebrafish, and indicated this mutant may serve as a potential model for ILFS1. Furthermore, we demonstrated that rapamycin treatment can partially rescue the liver defect in mutants, thus providing a practicable therapeutic plan for ILFS1.