Journal article

Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans

Joyce van de Leemput, Jayanth Chandran, Melanie A Knight, Lynne A Holtzclaw, Sonja Scholz, Mark R Cookson, Henry Houlden, Katrina Gwinn-Hardy, Hon-Chung Fung, Xian Lin, Dena Hernandez, Javier Simon-Sanchez, Nick W Wood, Paola Giunti, Ian Rafferty, John Hardy, Elsdon Storey, RJ McKinlay Gardner, Susan M Forrest, Elizabeth MC Fisher Show all

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2007

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 (Itpr1(Delta18/Delta18)), 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..

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Grants

Awarded by Medical Research Council


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Awarded by NATIONAL INSTITUTE ON AGING