Noonan syndrome-associated biallelic LZTR1 mutations cause cardiac hypertrophy and vascular malformations in zebrafish.

ABSTRACT:

Background

Variants in the LZTR1 (leucine-zipper-like transcription regulator 1) gene (OMIM #600574) have been reported in recessive Noonan syndrome patients. In vivo evidence from animal models to support its causative role is lacking.

Methods

By CRISPR-Cas9 genome editing, we generated lztr1-mutated zebrafish (Danio rerio). Analyses of histopathology and downstream signaling were performed to investigate the pathogenesis of cardiac and extracardiac abnormalities in Noonan syndrome.

Results

A frameshift deletion allele was created in the zebrafish lztr1. Crosses of heterozygotes obtained homozygous lztr1 null mutants that modeled LZTR1 loss-of-function. Histological analyses of the model revealed ventricular hypertrophy, the deleterious signature of Noonan syndrome-a

SUBMITTER: Nakagama Y 

PROVIDER: S-EPMC7057116 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature