Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice.

ABSTRACT: Germline pathogenic variants that activate the Ras/mitogen-activated protein kinase (MAPK) pathway cause neurodevelopmental disorders called 'Rasopathies'. Because many affected proteins directly regulate Ras, causative mutations may alter other Ras-dependent pathways in addition to MAPK signaling. To better understand which Rasopathy sequelae result from hyperactivation of downstream MAP kinases, we engineered mice with a gain-of-function mutation in the terminal MAP kinase gene Mapk1, which encodes ERK2 and is associated with the recently described genetic syndrome MAPK1-related Rasopathy (MRR). Mapk1 mutant mice successfully modeled key aspects of the human MRR phenotype, including small stature, facial dysmorphism, and impaired cognitive function. Importantly, they

SUBMITTER: Grover KE 

PROVIDER: S-EPMC12724492 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature