Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy

Abstract 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 inte...

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Autores principales:	Naresh K. Genabai, Annapoorna Kannan, Saif Ahmad, Xiaoting Jiang, Kanchan Bhatia, Laxman Gangwani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/efb0f422927b463e80d304db4c1a66bc
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spelling	oai:doaj.org-article:efb0f422927b463e80d304db4c1a66bc2021-12-02T12:32:07ZDeregulation of ZPR1 causes respiratory failure in spinal muscular atrophy10.1038/s41598-017-07603-z2045-2322https://doaj.org/article/efb0f422927b463e80d304db4c1a66bc2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07603-zhttps://doaj.org/toc/2045-2322Abstract 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.Naresh K. GenabaiAnnapoorna KannanSaif AhmadXiaoting JiangKanchan BhatiaLaxman GangwaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naresh K. Genabai Annapoorna Kannan Saif Ahmad Xiaoting Jiang Kanchan Bhatia Laxman Gangwani Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy
description	Abstract 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	article
author	Naresh K. Genabai Annapoorna Kannan Saif Ahmad Xiaoting Jiang Kanchan Bhatia Laxman Gangwani
author_facet	Naresh K. Genabai Annapoorna Kannan Saif Ahmad Xiaoting Jiang Kanchan Bhatia Laxman Gangwani
author_sort	Naresh K. Genabai
title	Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy
title_short	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_sort	deregulation of zpr1 causes respiratory failure in spinal muscular atrophy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/efb0f422927b463e80d304db4c1a66bc
work_keys_str_mv	AT nareshkgenabai deregulationofzpr1causesrespiratoryfailureinspinalmuscularatrophy AT annapoornakannan deregulationofzpr1causesrespiratoryfailureinspinalmuscularatrophy AT saifahmad deregulationofzpr1causesrespiratoryfailureinspinalmuscularatrophy AT xiaotingjiang deregulationofzpr1causesrespiratoryfailureinspinalmuscularatrophy AT kanchanbhatia deregulationofzpr1causesrespiratoryfailureinspinalmuscularatrophy AT laxmangangwani deregulationofzpr1causesrespiratoryfailureinspinalmuscularatrophy
_version_	1718394192533651456

Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy

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