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Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy
Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts wit...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557895/ https://www.ncbi.nlm.nih.gov/pubmed/28811488 http://dx.doi.org/10.1038/s41598-017-07603-z |
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author | Genabai, Naresh K. Kannan, Annapoorna Ahmad, Saif Jiang, Xiaoting Bhatia, Kanchan Gangwani, Laxman |
author_facet | Genabai, Naresh K. Kannan, Annapoorna Ahmad, Saif Jiang, Xiaoting Bhatia, Kanchan Gangwani, Laxman |
author_sort | Genabai, Naresh K. |
collection | PubMed |
description | Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts with SMN. ZPR1 is down regulated in SMA patients. We report that ZPR1 functions downstream of SMN to regulate HoxA5 levels in phrenic motor neurons that control respiration. Spatiotemporal inactivation of Zpr1 gene in motor neurons down-regulates HoxA5 and causes defects in the function of phrenic motor neurons that results in respiratory failure and perinatal lethality in mice. Modulation in ZPR1 levels directly correlates and influences levels of HoxA5 transcription. In SMA mice, SMN-deficiency causes down-regulation of ZPR1 and HoxA5 that result in degeneration of phrenic motor neurons. Identification of ZPR1 and HoxA5 as potential targets provides a paradigm for developing strategies to treat respiratory distress in SMA. |
format | Online Article Text |
id | pubmed-5557895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55578952017-08-16 Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy Genabai, Naresh K. Kannan, Annapoorna Ahmad, Saif Jiang, Xiaoting Bhatia, Kanchan Gangwani, Laxman Sci Rep Article Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts with SMN. ZPR1 is down regulated in SMA patients. We report that ZPR1 functions downstream of SMN to regulate HoxA5 levels in phrenic motor neurons that control respiration. Spatiotemporal inactivation of Zpr1 gene in motor neurons down-regulates HoxA5 and causes defects in the function of phrenic motor neurons that results in respiratory failure and perinatal lethality in mice. Modulation in ZPR1 levels directly correlates and influences levels of HoxA5 transcription. In SMA mice, SMN-deficiency causes down-regulation of ZPR1 and HoxA5 that result in degeneration of phrenic motor neurons. Identification of ZPR1 and HoxA5 as potential targets provides a paradigm for developing strategies to treat respiratory distress in SMA. Nature Publishing Group UK 2017-08-15 /pmc/articles/PMC5557895/ /pubmed/28811488 http://dx.doi.org/10.1038/s41598-017-07603-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Genabai, Naresh K. Kannan, Annapoorna Ahmad, Saif Jiang, Xiaoting Bhatia, Kanchan Gangwani, Laxman Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy |
title | Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy |
title_full | Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy |
title_fullStr | Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy |
title_full_unstemmed | Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy |
title_short | Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy |
title_sort | deregulation of zpr1 causes respiratory failure in spinal muscular atrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557895/ https://www.ncbi.nlm.nih.gov/pubmed/28811488 http://dx.doi.org/10.1038/s41598-017-07603-z |
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