ArticleThe American journal of pathology2003
Transgenic mice expressing mutant Notch3 develop vascular alterations characteristic of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Sex differences and risk factors for bleeding in Alagille syndrome.EMBO molecular medicine · 2022Pooled it
- Contribution of "Omic" Studies to the Understanding of Cadasil. A Systematic Review.International journal of molecular sciences · 2021Pooled it
- CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in cultured vascular smooth muscle cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2012Trial
- Review
- A review of animal models of vascular dementia.Molecular biology reports · 2026Review
- Age-dependent vascular and neurological characteristics of CADASIL are recapitulated in Notch3 mutant zebrafish, implicating a role for type IV collagen in disease progression.Acta neuropathologica communications · 2026Article
- Selective vulnerability of cerebral vasculature toScience advances · 2026Article
- NOTCH3 Mutations in CADASIL: a multicellular perspective on neurodegeneration.Cell communication and signaling : CCS · 2026Review
- Critical analysis of translational potential of rodent models of white matter pathology across a wide spectrum of human diseases.Cell death & disease · 2025Review
- Review
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Assessing changes on large cerebral arteries in CADASIL: Preliminary insights from a case-control analysis.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2025Observational
- Signaling pathways and molecular mechanisms involved in the onset and progression of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); a focus on Notch3 signaling.The journal of headache and pain · 2025Review
- The N-acetylglucosaminyltransferase Radical fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants.The Journal of biological chemistry · 2024Article
- MYPT1Translational stroke research · 2024Article
- Progress to Clarify HowBiomolecules · 2024Review
- Modeling of age-related neurological disease: utility of zebrafish.Frontiers in aging neuroscience · 2024Review
- Intracranial Aneurysms and Genetics: An Extensive Overview of Genomic Variations, Underlying Molecular Dynamics, Inflammatory Indicators, and Forward-Looking Insights.Brain sciences · 2023Review
- Exonic mutations in cell-cell adhesion may contribute to CADASIL-related CSVD pathology.Human genetics · 2023Article
- ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics.Acta neuropathologica communications · 2023Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an increasingly recognized adult-onset autosomal dominant vascular dementia, caused by highly stereotyped mutations in the Notch3 receptor. CADASIL is a widespread angiopathy characterized by a degeneration of vascular smooth muscle cells (VSMCs) and the abnormal accumulation of electron-dense granular material called GOM and Notch3 protein, because of an impaired clearance. Evidence that VSMCs are the primary target of the pathogenic process is supported by the restricted expression of Notch3 in these cells but mechanisms of their degeneration remain essentially unknown. We generated transgenic mice in which the SM22alpha promoter drove, in VSMCs, the expression of a full-length human Notch3 carrying the Arg90Cys mutation, a CADASIL archetypal mutation. Transgenic mice showed no evidence of prominent brain parenchyma damage but demonstrated the two hallmarks of the CADASIL angiopathy, GOM deposits and Notch3 accumulation, within both the cerebral and peripheral arteries. Of interest, arteries of the tail were more severely affected with prominent signs of VSMC degeneration. Time-course analysis of vessel changes revealed that disruption of normal VSMC anchorage to adjacent extracellular matrix and cells, VSMC cytoskeleton changes as well as starting signs of VSMC degeneration, which were detected around 10 months of age, preceded Notch3 and GOM accumulation appearance, which were observed only by 14 to 16 months of age. In conclusion, we have generated transgenic mice that recapitulate the characteristic vascular lesions observed in CADASIL. Our results indicate that Notch3 or GOM accumulation are unlikely to be the prerequisites for the induction of VSMC degeneration and suggest that degeneration of VSMCs may rather be triggered by the disruption of their normal anchorage, based on the important role of adhesion for cell survival.
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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.