title: An animal model for the molecular genetics of CADASIL. (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).
abstract: BACKGROUND
  CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inherited condition that causes repeated small-scale strokes in adults. CADASIL is caused only by mutations in the human NOTCH3 gene that increase or decrease the number of cysteines within the epidermal growth factor (EGF) repeats of the NOTCH3 protein. Drosophila: lethal-Abruptex is a similar condition because it is also caused only by mutations that increase or decrease the number of cysteines within the EGF repeat portion of the Notch protein.
  
  
  RESULTS
  Drosophila: lethal-Abruptex and human CADASIL are precisely analogous at the molecular level, and both are genetically dominant. These precise similarities, together with the fact that the structure and function of Notch has been highly conserved throughout the animal kingdom, provide an animal model for the molecular and genetic aspects of human CADASIL. It also provides support for Spinner's proposal that CADASIL results from dominant inhibition of the Notch pathway.
  
  
  CONCLUSIONS
  Because the phenotypes of Notch mutations are cell-autonomous, the symptoms of CADASIL indicate that adult vascular smooth muscle cells require the continuing function of the NOTCH3 pathway in the adult. For this reason, further analysis of the NOTCH3 pathway may provide more general insights into the biology of vascular smooth muscle cells. In the case of CADASIL, the powerful genetic tools available in Drosophila: should help to facilitate future research.
authors.affiliation: Department of Biology, George Mason University, Fairfax, VA 22030, USA. kfryxell@gmu.edu
authors.forename: K J
authors.initials: KJ
authors.lastname: Fryxell
authors.forename: M
authors.initials: M
authors.lastname: Soderlund
authors.forename: T V
authors.initials: TV
authors.lastname: Jordan
mesh_terms: D000818:Animals; D001001:Anura; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D001160:Arterioles / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D015161:Dementia, Multi-Infarct / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics; D005799:Genes, Dominant; D005804:Genes, Lethal; D008040:Genetic Linkage; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009218:Myosins / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics
chemical_list: C499374:NOTCH3 protein, human; C499373:Notch3 protein, mouse; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C073572:Notch4 protein, mouse; D004815:Epidermal Growth Factor; D003094:Collagen; D009218:Myosins; D003545:Cysteine