ArticleDisease models & mechanisms2022
MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Muscle ultrasonography in costello syndrome: unveiling new clinical insights of a complex muscular phenotype.Orphanet journal of rare diseases · 2026Article
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- RAS/ERK signaling and PLK1: Coordinating developmental regulation and disease mechanisms.Current opinion in cell biology · 2025Review
- Impaired MC3T3-E1 osteoblast differentiation triggered by oncogenic HRAS is rescued by the farnesyltransferase inhibitor Tipifarnib.Scientific reports · 2025Article
- Recurrent p.H119Y variant in MAP2K1 expands the phenotypic spectrum of MAP2K1 -related RASopathy.American journal of medical genetics. Part A · 2025Article
- RASopathies - what they reveal about RAS/MAPK signaling in skeletal muscle development.Disease models & mechanisms · 2024Review
- RASopathies - what they reveal about RAS/MAPK signaling in skeletal muscle development.Disease models & mechanisms · 2024Review
- Article
- Skeletal defects and bone metabolism in Noonan, Costello and cardio-facio-cutaneous syndromes.Frontiers in endocrinology · 2023Review
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- Defining RASopathy.Disease models & mechanisms · 2022Article
- Understanding and drugging RAS: 40 years to break the tip of the iceberg.Disease models & mechanisms · 2022Article
- How can same-gene mutations promote both cancer and developmental disorders?Science advances · 2022Article
- Multidisciplinary Management of Costello Syndrome: Current Perspectives.Journal of multidisciplinary healthcare · 2022Review
- Increased osteoclastogenesis contributes to bone loss in the Costello syndromeFrontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes caused by mutations within various components of the Ras/MAPK pathway. An important part of the phenotype that greatly impacts quality of life is hypotonia. To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized. We identified a skeletal myopathy that was due, in part, to inhibition of embryonic myogenesis and myofiber formation, resulting in a reduction in myofiber size and number that led to reduced muscle mass and strength. In addition to hyperactivation of the Ras/MAPK and PI3K/AKT pathways, there was a significant reduction in p38 signaling, as well as global transcriptional alterations consistent with the myopathic phenotype. Inhibition of Ras/MAPK pathway signaling using a MEK inhibitor rescued the HrasG12V myopathy phenotype both in vitro and in vivo, demonstrating that increased MAPK signaling is the main cause of the muscle phenotype in CS.
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Registered trials
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