The neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1) affects the cerebellum and inferior olive, though previous research has focused primarily on the cerebellum. As a result, it is unknown what molecular alterations are present in the inferior olive, and whether these changes are found in other affected tissues. This study addresses these questions for the first time using two different SCA1 mouse models. We found that differentially regulated genes in the inferior olive segregated into several biological pathways. Comparison of the inferior olive and cerebellum demonstrates that vulnerable tissues in SCA1 are not uniform in their gene expression changes, and express largely discrete but some commonly enriched biological pathways. Importantly, we also found that brain region-specific differences occur early in disease initiation and progression, and they are shared across the two mouse models of SCA1. This suggests different mechanisms of degeneration at work in the inferior olive and cerebellum.
RNA sequencing data have been deposited in GEO under accession (number: 122099).
Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1NCBI Gene Expression Omnibus, GSE122099.
Expression data from early symptomatic Sca1154Q/2Q and Sca7266Q/5Q knock-in cerebellumNCBI Gene Expression Omnibus, GSE9914.
Cerebellar RNA-Seq from ATXN1 Transgenic Mice Reveals SCA1 Disease Progression and Protection PathwaysNCBI Gene Expression Omnibus, GSE75778.
- Janghoo Lim
- Janghoo Lim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2016-11342) of the Yale University. The Yale University Institutional Animal Care and Use Committee approved all research and animal care procedures. We made every effort to minimize animal suffering.
- J Paul Taylor, St Jude Children's Research Hospital, United States
© 2018, Driessen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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