Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Disease modeling with human neurons reveals LMNB1 dysregulation underlying DYT1 dystonia

View ORCID ProfileBaojin Ding, View ORCID ProfileYu Tang, Shuaipeng Ma, Masuma Akter, Meng-Lu Liu, Tong Zang, Chun-Li Zhang
doi: https://doi.org/10.1101/2020.08.11.246371
Baojin Ding
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
2Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette LA 70503, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Baojin Ding
  • For correspondence: Baojin.Ding@Louisiana.edu Chun-Li.Zhang@utsouthwestern.edu
Yu Tang
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
3National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yu Tang
Shuaipeng Ma
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masuma Akter
2Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette LA 70503, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Meng-Lu Liu
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tong Zang
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chun-Li Zhang
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Baojin.Ding@Louisiana.edu Chun-Li.Zhang@utsouthwestern.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

DYT1 dystonia is a hereditary neurological disease caused by a heterozygous mutation in torsin A (TOR1A). While animal models provide insights into disease mechanisms, significant species-dependent differences exist since mice with the identical heterozygous mutation fail to show pathology. Here, we model DYT1 by using human patient-derived motor neurons. These neurons with the heterozygous TOR1A mutation show markedly thickened nuclear lamina, disrupted nuclear morphology, and impaired nucleocytoplasmic transport, whereas they lack the perinuclear “blebs” that are often observed in animal models. Importantly, we further uncover that the nuclear lamina protein LMNB1 is specifically dysregulated in expression and subcellular localization. LMNB1 downregulation can largely ameliorate all the cellular defects in DYT1 motor neurons. These results reveal the value of disease modeling with human neurons and provide novel molecular mechanisms underlying DYT1 dystonia and potentially other neurological diseases with impaired nucleocytoplasmic transport.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵5 Lead contact

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted August 12, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Disease modeling with human neurons reveals LMNB1 dysregulation underlying DYT1 dystonia
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Disease modeling with human neurons reveals LMNB1 dysregulation underlying DYT1 dystonia
Baojin Ding, Yu Tang, Shuaipeng Ma, Masuma Akter, Meng-Lu Liu, Tong Zang, Chun-Li Zhang
bioRxiv 2020.08.11.246371; doi: https://doi.org/10.1101/2020.08.11.246371
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Disease modeling with human neurons reveals LMNB1 dysregulation underlying DYT1 dystonia
Baojin Ding, Yu Tang, Shuaipeng Ma, Masuma Akter, Meng-Lu Liu, Tong Zang, Chun-Li Zhang
bioRxiv 2020.08.11.246371; doi: https://doi.org/10.1101/2020.08.11.246371

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4230)
  • Biochemistry (9123)
  • Bioengineering (6766)
  • Bioinformatics (23968)
  • Biophysics (12109)
  • Cancer Biology (9509)
  • Cell Biology (13753)
  • Clinical Trials (138)
  • Developmental Biology (7622)
  • Ecology (11674)
  • Epidemiology (2066)
  • Evolutionary Biology (15490)
  • Genetics (10630)
  • Genomics (14310)
  • Immunology (9473)
  • Microbiology (22821)
  • Molecular Biology (9086)
  • Neuroscience (48914)
  • Paleontology (355)
  • Pathology (1480)
  • Pharmacology and Toxicology (2566)
  • Physiology (3839)
  • Plant Biology (8322)
  • Scientific Communication and Education (1468)
  • Synthetic Biology (2295)
  • Systems Biology (6180)
  • Zoology (1299)