Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1

Abstract
Data availability
Article and author information
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Abstract

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.

Data availability

RNA sequencing data have been deposited in GEO under accession (number: 122099).

The following data sets were generated

1. Driessen TM
2. Lee PJ
3. Lim J
(2018) Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1
NCBI Gene Expression Omnibus, GSE122099.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122099

The following previously published data sets were used

1. Gatchel JR
2. Watase K
3. Thaller C
4. Carson JP
5. Jafar-Nejad P
6. Shaw CA
7. Zu T
8. Orr HT
9. Zoghbi HY
(2007) Expression data from early symptomatic Sca1154Q/2Q and Sca7266Q/5Q knock-in cerebellum
NCBI Gene Expression Omnibus, GSE9914.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9914
1. Ingram M
2. Leathley E
3. Henzler C
4. Duvick L
5. Yang R
6. Bergmann P
7. Zoghbi HY
8. Orr HT
(2016) Cerebellar RNA-Seq from ATXN1 Transgenic Mice Reveals SCA1 Disease Progression and Protection Pathways
NCBI Gene Expression Omnibus, GSE75778.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75778

Article and author information

Author details

Terri M Driessen

Department of Genetics, Yale School of Medicine, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Paul J Lee

Department of Genetics, Yale School of Medicine, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Janghoo Lim

Department of Genetics, Yale School of Medicine, New Haven, United States

For correspondence
janghoo.lim@yale.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5331-210X

Funding

National Institute of Neurological Disorders and Stroke (NS083706)

Janghoo Lim

National Institute of Neurological Disorders and Stroke (NS088321)

Janghoo Lim

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

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.

Copyright

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.