Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy.

ABSTRACT:

Background

Biallelic pathogenic variants of LARS1 cause infantile liver failure syndrome type 1 (ILFS1), which is characterized by acute hepatic failure with steatosis in infants. LARS functions as a protein associated with mTORC1 and plays a crucial role in amino acid-triggered mTORC1 activation and regulation of autophagy. A previous study demonstrated that larsb-knockout zebrafish exhibit conditions resembling ILFS. However, a comprehensive analysis of larsb-knockout zebrafish has not yet been performed because of early mortality.

Methods

We generated a long-term viable zebrafish model carrying a LARS1 variant identified in an ILFS1 patient (larsb-I451F zebrafish) and analyzed the pathogenesis of the affected liver of ILFS1.

Results

Hepatic dysfunction is most prom

SUBMITTER: Inoue M 

PROVIDER: S-EPMC11134648 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature