Inducible knockout of Clec16a in mice results in sensory neurodegeneration

Abstract CLEC16A has been shown to play a role in autophagy/mitophagy processes. Additionally, genetic variants in CLEC16A have been implicated in multiple autoimmune diseases. We generated an inducible whole-body knockout, Clec16a ΔUBC mice, to investigate the loss of function of CLEC16A. The mice...

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Autores principales:	Heather S. Hain, Rahul Pandey, Marina Bakay, Bryan P. Strenkowski, Danielle Harrington, Micah Romer, William W. Motley, Jian Li, Eunjoo Lancaster, Lindsay Roth, Judith B. Grinspan, Steven S. Scherer, Hakon Hakonarson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b104a7aa9a7427988082d3423e2cc80
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spelling	oai:doaj.org-article:9b104a7aa9a7427988082d3423e2cc802021-12-02T16:55:25ZInducible knockout of Clec16a in mice results in sensory neurodegeneration10.1038/s41598-021-88895-02045-2322https://doaj.org/article/9b104a7aa9a7427988082d3423e2cc802021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88895-0https://doaj.org/toc/2045-2322Abstract CLEC16A has been shown to play a role in autophagy/mitophagy processes. Additionally, genetic variants in CLEC16A have been implicated in multiple autoimmune diseases. We generated an inducible whole-body knockout, Clec16a ΔUBC mice, to investigate the loss of function of CLEC16A. The mice exhibited a neuronal phenotype including tremors and impaired gait that rapidly progressed to dystonic postures. Nerve conduction studies and pathological analysis revealed loss of sensory axons that are associated with this phenotype. Activated microglia and astrocytes were found in regions of the CNS. Several mitochondrial-related proteins were up- or down-regulated. Upregulation of interferon stimulated gene 15 (IGS15) were observed in neuronal tissues. CLEC16A expression inversely related to IGS15 expression. ISG15 may be the link between CLEC16A and downstream autoimmune, inflammatory processes. Our results demonstrate that a whole-body, inducible knockout of Clec16a in mice results in an inflammatory neurodegenerative phenotype resembling spinocerebellar ataxia.Heather S. HainRahul PandeyMarina BakayBryan P. StrenkowskiDanielle HarringtonMicah RomerWilliam W. MotleyJian LiEunjoo LancasterLindsay RothJudith B. GrinspanSteven S. SchererHakon HakonarsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heather S. Hain Rahul Pandey Marina Bakay Bryan P. Strenkowski Danielle Harrington Micah Romer William W. Motley Jian Li Eunjoo Lancaster Lindsay Roth Judith B. Grinspan Steven S. Scherer Hakon Hakonarson Inducible knockout of Clec16a in mice results in sensory neurodegeneration
description	Abstract CLEC16A has been shown to play a role in autophagy/mitophagy processes. Additionally, genetic variants in CLEC16A have been implicated in multiple autoimmune diseases. We generated an inducible whole-body knockout, Clec16a ΔUBC mice, to investigate the loss of function of CLEC16A. The mice exhibited a neuronal phenotype including tremors and impaired gait that rapidly progressed to dystonic postures. Nerve conduction studies and pathological analysis revealed loss of sensory axons that are associated with this phenotype. Activated microglia and astrocytes were found in regions of the CNS. Several mitochondrial-related proteins were up- or down-regulated. Upregulation of interferon stimulated gene 15 (IGS15) were observed in neuronal tissues. CLEC16A expression inversely related to IGS15 expression. ISG15 may be the link between CLEC16A and downstream autoimmune, inflammatory processes. Our results demonstrate that a whole-body, inducible knockout of Clec16a in mice results in an inflammatory neurodegenerative phenotype resembling spinocerebellar ataxia.
format	article
author	Heather S. Hain Rahul Pandey Marina Bakay Bryan P. Strenkowski Danielle Harrington Micah Romer William W. Motley Jian Li Eunjoo Lancaster Lindsay Roth Judith B. Grinspan Steven S. Scherer Hakon Hakonarson
author_facet	Heather S. Hain Rahul Pandey Marina Bakay Bryan P. Strenkowski Danielle Harrington Micah Romer William W. Motley Jian Li Eunjoo Lancaster Lindsay Roth Judith B. Grinspan Steven S. Scherer Hakon Hakonarson
author_sort	Heather S. Hain
title	Inducible knockout of Clec16a in mice results in sensory neurodegeneration
title_short	Inducible knockout of Clec16a in mice results in sensory neurodegeneration
title_full	Inducible knockout of Clec16a in mice results in sensory neurodegeneration
title_fullStr	Inducible knockout of Clec16a in mice results in sensory neurodegeneration
title_full_unstemmed	Inducible knockout of Clec16a in mice results in sensory neurodegeneration
title_sort	inducible knockout of clec16a in mice results in sensory neurodegeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b104a7aa9a7427988082d3423e2cc80
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_version_	1718382877452795904

Inducible knockout of Clec16a in mice results in sensory neurodegeneration

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