ArticleThe Journal of clinical investigation2004
Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 240 papers, 1 of them a synthesis that pooled it.
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Who cites it
240 citing papers in PubMed, 1 synthesis or guideline pooled it, 394 citations in OpenAlex.
- Skeletal muscle alterations in Marfan syndrome: a systematic review.Journal of muscle research and cell motility · 2025Pooled it
- Differential contribution of elastin and fibrillin-1 to the cardiovascular phenotype of a double heterozygous Marfan and Williams-Beuren syndrome mouse model.Genes & diseases · 2027Article
- Genotype-associated structural and nanomechanical alterations of aortic fibrillin-1 microfibrils in Marfan syndrome.Matrix biology plus · 2026Article
- Introducing Allopurinol to the Medical Treatment of Marfan Syndrome: Advantages, Limitations, and Potential Extension to other Aortopathies.Cardiovascular drugs and therapy · 2026Review
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Lymphatic dysfunction and ZFP36 deficiency contribute to myxomatous valve degeneration in Marfan syndrome mice.The Journal of clinical investigation · 2026Article
- Hypertension drives thoracic aortic aneurysm and dissection in male, but not female, Marfan mice.Journal of the mechanical behavior of biomedical materials · 2026Article
- Fibronectin-induced overactivation of αNature communications · 2026Article
- Immune Mechanisms of Heart Valve Development, Homeostasis, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Growth arrest of thoracic aortic aneurysms in aging Marfan mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Angiotensin II Induces Abdominal Aortic Branch Aneurysms inArteriosclerosis, thrombosis, and vascular biology · 2026Article
- Article
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Pain Hypersensitivity in a Mouse Model of Marfan Syndrome.Antioxidants (Basel, Switzerland) · 2026Article
- Transcription regulation by TBX18 in smooth muscle cells is essential for normal aortic development and homeostasis.Cardiovascular research · 2025Article
- A Marfan-Associated FBN1 Nonsense Mutation Mouse Model Reveals Adventitial Inflammation During Aneurysm Progression.bioRxiv : the preprint server for biology · 2025Article
- Perivascular inflammation in the progression of aortic aneurysms in Marfan syndrome.JCI insight · 2025Article
- Atherosclerotic Plaque Instability and Rupture: Recommended Mouse Models to Empower Clinically Relevant Discoveries, Diagnostics, and Therapeutics.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Importance of localized dilatation and distensibility in identifying determinants of thoracic aortic aneurysm with neural operators.PLoS computational biology · 2025Article
- Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure.Scientific reports · 2025Article
180 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Marfan syndrome is a connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1). A dominant-negative mechanism has been inferred based upon dominant inheritance, mulitimerization of monomers to form microfibrils, and the dramatic paucity of matrix-incorporated fibrillin-1 seen in heterozygous patient samples. Yeast artificial chromosome-based transgenesis was used to overexpress a disease-associated mutant form of human fibrillin-1 (C1663R) on a normal mouse background. Remarkably, these mice failed to show any abnormalities of cellular or clinical phenotype despite regulated overexpression of mutant protein in relevant tissues and developmental stages and direct evidence that mouse and human fibrillin-1 interact with high efficiency. Immunostaining with a human-specific mAb provides what we believe to be the first demonstration that mutant fibrillin-1 can participate in productive microfibrillar assembly. Informatively, use of homologous recombination to generate mice heterozygous for a comparable missense mutation (C1039G) revealed impaired microfibrillar deposition, skeletal deformity, and progressive deterioration of aortic wall architecture, comparable to characteristics of the human condition. These data are consistent with a model that invokes haploinsufficiency for WT fibrillin-1, rather than production of mutant protein, as the primary determinant of failed microfibrillar assembly. In keeping with this model, introduction of a WT FBN1 transgene on a heterozygous C1039G background rescues aortic phenotype.
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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.