title: Is the SHRSP [corrected] strain a suitable model of spontaneous CADASIL?
abstract: A number of features of the pathology occurring in spontaneously hypertensive stroke prone rats (SHRSPs), such as MRI brain signal abnormalities, the presence of high protein content in cerebrospinal fluid and vessel wall thickening, seem to indicate that this strain is a suitable model for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To explore this hypothesis, we sought the human diagnostic hallmarks of the disease [the accumulation of granular osmiophilic material (GOM) deposits in vessel walls and NOTCH3 gene mutations] in SHRSPs. Male SHRSPs fed a permissive diet were sacrificed 3 days after the first MRI visualisation of brain abnormalities. Whole blood and kidney samples were respectively collected for molecular and electron microscopy evaluations. Automated sequence analysis of exons and intron-exon boundaries did not reveal any genetic variation in the NOTCH3 gene, and electron microscopy excluded the presence of GOM. The findings of this study exclude SHRSPs as a possible model for CADASIL.
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.forename: Paolo
authors.initials: P
authors.lastname: Gelosa
authors.forename: Silvana
authors.initials: S
authors.lastname: Pileggi
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marocchi
authors.forename: Uliano
authors.initials: U
authors.lastname: Guerrini
authors.forename: Alice
authors.initials: A
authors.lastname: Pignieri
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D046589:CADASIL / Q000235:genetics; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000648:ultrastructure; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D050533:Glomerular Basement Membrane / Q000737:chemistry / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009993:Osmium Tetroxide; D011507:Proteinuria / Q000235:genetics / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011922:Rats, Mutant Strains / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000633:toxicity; D013194:Staining and Labeling; D020521:Stroke / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: C499374:NOTCH3 protein, human; C498556:Notch3 protein, rat; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D017673:Sodium Chloride, Dietary; D009993:Osmium Tetroxide