New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to β-adrenergic stimulation-induced cardiac fibrosis.

ABSTRACT:

Background

Noonan syndrome (NS) is a genetic disorder characterized by short stature, a distinctive facial appearance, and heart defects. We recently discovered a novel NS gene, RIT1, which is a member of the RAS subfamily of small GTPases. NS patients with RIT1 mutations have a high incidence of hypertrophic cardiomyopathy and edematous phenotype, but the specific role of RIT1 remains unclear.

Methods

To investigate how germline RIT1 mutations cause NS, we generated knock-in mice that carried a NS-associated Rit1 A57G mutation (Rit1^A57G/+). We investigated the phenotypes of Rit1^A57G/+ mice in fetal and adult stages as well as the effects of isoproterenol on cardiac function in Rit1^A57G/+ mice.

Findings

Rit1^A57G/+ embryos ex

SUBMITTER: Takahara S 

PROVIDER: S-EPMC6491386 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature