RASopathies in Cardiac Disease.

RASopathies are a group of clinically overlapping autosomal dominant disorders caused primarily by mutations in genes that reside along the canonical Ras-mitogen-activated protein kinase signaling cascade. Though individually rare, collectively, these disorders constitute one of the largest families of congenital disorders worldwide, particularly for infantile hypertrophic cardiomyopathy. Significantly, despite almost five decades of RASopathy research, therapeutic options remain limited and focused primarily on treating symptoms rather than disease etiology.

Increased osteoclastogenesis contributes to bone loss in the Costello syndrome mouse model.

RAS GTPases are ubiquitous GDP/GTP-binding proteins that function as molecular switches in cellular signalling and control numerous signalling pathways and biological processes. Pathogenic mutations in genes severely affect cellular homeostasis, leading to cancer when occurring in somatic cells and developmental disorders when the germline is affected. These disorders are generally termed as RASopathies and among them Costello syndrome (CS) is a distinctive entity that is caused by specific germline mutations.

Mitochondria and the future of RASopathies: the emergence of bioenergetics.

RASopathies are a family of rare autosomal dominant disorders that affect the canonical Ras/MAPK signaling pathway and manifest as neurodevelopmental systemic syndromes, including Costello syndrome (CS). In this issue of the JCI, Dard et al. describe the molecular determinants of CS using a myriad of genetically modified models, including mice expressing HRAS p.

Studying Metabolic Abnormalities in the Costello Syndrome HRAS G12V Mouse Model: Isolation of Mouse Embryonic Fibroblasts and Their In Vitro Adipocyte Differentiation.

Costello syndrome (CS), characterized by a developmental delay and a failure to thrive, is also associated with an impaired lipid and energy metabolism. White adipose tissue is a central sensor of whole-body energy homeostasis, and HRAS hyperactivation may affect adipocyte differentiation and mature adipocyte homeostasis. An extremely useful tool for delineating in vitro intrinsic cellular signaling leading to metabolic alterations during adipogenesis is mouse embryonic fibroblasts, known to differentiate into adipocytes in response to adipogenesis-stimulating factors.