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Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells
Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no det...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944495/ https://www.ncbi.nlm.nih.gov/pubmed/24487409 http://dx.doi.org/10.1242/dmm.014050 |
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author | Kong, Xiang Y. Nesset, Cecilie Kasi Damme, Markus Løberg, Else-Marit Lübke, Torben Mæhlen, Jan Andersson, Kristin B. Lorenzo, Petra I. Roos, Norbert Thoresen, G. Hege Rustan, Arild C. Kase, Eili T. Eskild, Winnie |
author_facet | Kong, Xiang Y. Nesset, Cecilie Kasi Damme, Markus Løberg, Else-Marit Lübke, Torben Mæhlen, Jan Andersson, Kristin B. Lorenzo, Petra I. Roos, Norbert Thoresen, G. Hege Rustan, Arild C. Kase, Eili T. Eskild, Winnie |
author_sort | Kong, Xiang Y. |
collection | PubMed |
description | Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1(gt/gt) mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1(gt/gt) liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1(gt/gt) Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1(gt/gt) mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage. |
format | Online Article Text |
id | pubmed-3944495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-39444952014-03-10 Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells Kong, Xiang Y. Nesset, Cecilie Kasi Damme, Markus Løberg, Else-Marit Lübke, Torben Mæhlen, Jan Andersson, Kristin B. Lorenzo, Petra I. Roos, Norbert Thoresen, G. Hege Rustan, Arild C. Kase, Eili T. Eskild, Winnie Dis Model Mech Research Article Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1(gt/gt) mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1(gt/gt) liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1(gt/gt) Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1(gt/gt) mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage. The Company of Biologists Limited 2014-03 2014-01-30 /pmc/articles/PMC3944495/ /pubmed/24487409 http://dx.doi.org/10.1242/dmm.014050 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Kong, Xiang Y. Nesset, Cecilie Kasi Damme, Markus Løberg, Else-Marit Lübke, Torben Mæhlen, Jan Andersson, Kristin B. Lorenzo, Petra I. Roos, Norbert Thoresen, G. Hege Rustan, Arild C. Kase, Eili T. Eskild, Winnie Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells |
title | Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells |
title_full | Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells |
title_fullStr | Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells |
title_full_unstemmed | Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells |
title_short | Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells |
title_sort | loss of lysosomal membrane protein ncu-g1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in kupffer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944495/ https://www.ncbi.nlm.nih.gov/pubmed/24487409 http://dx.doi.org/10.1242/dmm.014050 |
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