Please use this identifier to cite or link to this item:
http://hdl.handle.net/10261/3579
Share/Export:
![]() ![]() |
|
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Title: | Deletion at ITPR1 Underlies Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans |
Authors: | van 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 CSIC; 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. | Issue Date: | 22-Jun-2007 | Publisher: | Public Library of Science | Citation: | PLoS Genet. 2007 June; 3(6): e108 | Abstract: | We 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. | URI: | http://hdl.handle.net/10261/3579 | DOI: | 10.1371/journal.pgen.0030108 | ISSN: | 1553-7404 |
Appears in Collections: | (IBV) Artículos |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
picrender.pdf | Principal | 355,05 kB | Adobe PDF | ![]() View/Open |
pgen.0030108.sg001.tif | Figure S1: Schematic of Genotyping Results across Mouse Chromosome 6 in Affected Mice | 10,18 MB | TIFF | ![]() View/Open |
pgen.0030108.sg002.tif | Figure S2: Sequence of Exon 36 of Itpr1 from Four Mice | 5,15 MB | TIFF | ![]() View/Open |
pgen.0030108.sg003.tif | Figure S3: Additional Families Harboring Deletion at the SCA15 Locus | 6,83 MB | TIFF | ![]() View/Open |
pgen.0030108.sg004.tif | Figure S4: Deleted Regions Identified in Families AUS1 and H27 | 876,45 kB | TIFF | ![]() View/Open |
Comentario_figuras.pdf | Archivo adicional 1 | 15,35 kB | Adobe PDF | ![]() View/Open |
Review this work
PubMed Central
Citations
111
checked on May 13, 2022
SCOPUSTM
Citations
228
checked on May 15, 2022
WEB OF SCIENCETM
Citations
186
checked on May 15, 2022
Page view(s)
391
checked on May 16, 2022
Download(s)
776
checked on May 16, 2022
Google ScholarTM
Check
Altmetric
Dimensions
Related articles:
WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.