English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/3579
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Deletion at ITPR1 Underlies Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans

Autorvan de Leemput, Joyce; Chandran, Jayanth; Knight, Melanie A.; Holtzclaw, Lynne A.; Scholz, Sonja; Cookson, Mark R.; Houlden, Henry; Gwinn-Hardy, Katrina; Fung, Hon-Chung; Lin, Xian; Hernández, Dena; Simón-Sánchez, Javier ; Wood, Nick W.; Giunti, Paola; Rafferty, Ian; Hardy, John; Storey, Elsdon; McKinlay Gardner, R. J.; Forrest, Susan M.; Fisher, Elizabeth M. C.; Russell, James T.; Cai, Huaibin; Singleton, Andrew B.
Fecha de publicación22-jun-2007
EditorPublic Library of Science
CitaciónPLoS Genet. 2007 June; 3(6): e108
ResumenWe observed a severe autosomal recessive movement disorder in mice used within our laboratory. We pursued a series of experiments to define the genetic lesion underlying this disorder and to identify a cognate disease in humans with mutation at the same locus. Through linkage and sequence analysis we show here that this disorder is caused by a homozygous in-frame 18-bp deletion in Itpr1 (Itpr1Δ18/Δ18), encoding inositol 1,4,5-triphosphate receptor 1. A previously reported spontaneous Itpr1 mutation in mice causes a phenotype identical to that observed here. In both models in-frame deletion within Itpr1 leads to a decrease in the normally high level of Itpr1 expression in cerebellar Purkinje cells. Spinocerebellar ataxia 15 (SCA15), a human autosomal dominant disorder, maps to the genomic region containing ITPR1; however, to date no causal mutations had been identified. Because ataxia is a prominent feature in Itpr1 mutant mice, we performed a series of experiments to test the hypothesis that mutation at ITPR1 may be the cause of SCA15. We show here that heterozygous deletion of the 5′ part of the ITPR1 gene, encompassing exons 1–10, 1–40, and 1–44 in three studied families, underlies SCA15 in humans.
Aparece en las colecciones: (IBV) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
picrender.pdfPrincipal355,05 kBAdobe PDFVista previa
pgen.0030108.sg001.tifFigure S1: Schematic of Genotyping Results across Mouse Chromosome 6 in Affected Mice10,18 MBTIFFVista previa
pgen.0030108.sg002.tifFigure S2: Sequence of Exon 36 of Itpr1 from Four Mice5,15 MBTIFFVista previa
pgen.0030108.sg003.tifFigure S3: Additional Families Harboring Deletion at the SCA15 Locus6,83 MBTIFFVista previa
pgen.0030108.sg004.tifFigure S4: Deleted Regions Identified in Families AUS1 and H27876,45 kBTIFFVista previa
Comentario_figuras.pdfArchivo adicional 115,35 kBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.