ArticleThe Journal of clinical investigation2008
A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 111 citations in OpenAlex.
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- Drugging Ras trafficking-are there new roads to travel?npj drug discovery · 2025Review
- Thyroid C-Cell Biology and Oncogenic Transformation.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- An Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathies.Cardiovascular drugs and therapy · 2023Review
- Quantitative proteomic profiling identifies global protein network dynamics in murine embryonic heart development.Developmental cell · 2023Article
- Deletion of Small GTPase H-Ras Rescues Memory Deficits and Reduces Amyloid Plaque-Associated Dendritic Spine Loss in Transgenic Alzheimer's Mice.Molecular neurobiology · 2023Article
- Article
- HRAS germline mutations impair LKB1/AMPK signaling and mitochondrial homeostasis in Costello syndrome models.The Journal of clinical investigation · 2022Article
- MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model.Disease models & mechanisms · 2022Article
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- Increased osteoclastogenesis contributes to bone loss in the Costello syndromeFrontiers in cell and developmental biology · 2022Article
- Review
- Ras isoform-specific expression, chromatin accessibility, and signaling.Biophysical reviews · 2021Review
- Evidence of Cooperation between Hippo Pathway andCancers · 2021Article
- Algorithmic assessment of cellular senescence in experimental and clinical specimens.Nature protocols · 2021Article
- 40 Years of RAS-A Historic Overview.Genes · 2021Review
- Review
- Studying Metabolic Abnormalities in the Costello Syndrome HRAS G12V Mouse Model: Isolation of Mouse Embryonic Fibroblasts and Their In Vitro Adipocyte Differentiation.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Genetic and Proteomic Contributions to the Pathophysiology of Moyamoya Angiopathy and Related Vascular Diseases.The application of clinical genetics · 2021Review
- Zebrafish Cancer Predisposition Models.Frontiers in cell and developmental biology · 2021Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin-Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.