ITPR1 Deletion Causes Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans
Author Information
Author(s): 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, Hernandez Dena, Simon-Sanchez Javier, Wood Nick W, Giunti Paola, Rafferty Ian, Hardy John, Storey Elsdon, Gardner R. J. McKinlay, Forrest Susan M, Fisher Elizabeth M. C, Russell James T, Cai Huaibin, Singleton Andrew B
Primary Institution: National Institute on Aging, National Institutes of Health
Hypothesis
Mutation at ITPR1 may be the cause of SCA15.
Conclusion
The study shows that deletion at the ITPR1 locus underlies ataxia in mice and spinocerebellar ataxia 15 in humans.
Supporting Evidence
- Deletion of ITPR1 was identified in three affected families.
- ITPR1 mutations lead to decreased protein levels in affected individuals.
- Similar movement disorders were observed in mice with ITPR1 deletions.
Takeaway
Scientists found that a missing piece in a gene called ITPR1 makes mice have trouble moving, and this same problem happens in some people.
Methodology
The researchers used genome-wide linkage analysis and sequencing to identify the genetic deletion in mice and humans.
Limitations
The small number of aged Itpr1wt/Δ18 animals limits the ability to examine subtle signs similar to those seen in SCA15 patients.
Participant Demographics
Affected family members were of Australian Anglo-Celtic origin.
Digital Object Identifier (DOI)
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