Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells

Kong XY, Nesset CK, Damme M, Loeberg E-M, Lübke T, Maehlen J, Andersson KB, Roos N, Thoresen GH, Rustan AC, Kase ET, et al. (2014)
Disease Models & Mechanisms 7(3): 351-362.

Download
OA
Journal Article | Published | English
Author
; ; ; ; ; ; ; ; ; ; ;
All
Abstract
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-g1gt/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-g1gt/gt liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1gt/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-g1gt/gt mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.
Keywords
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

Kong XY, Nesset CK, Damme M, et al. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms. 2014;7(3):351-362.
Kong, X. Y., Nesset, C. K., Damme, M., Loeberg, E. - M., Lübke, T., Maehlen, J., Andersson, K. B., et al. (2014). Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms, 7(3), 351-362.
Kong, X. Y., Nesset, C. K., Damme, M., Loeberg, E. - M., Lübke, T., Maehlen, J., Andersson, K. B., Roos, N., Thoresen, G. H., Rustan, A. C., et al. (2014). Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms 7, 351-362.
Kong, X.Y., et al., 2014. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms, 7(3), p 351-362.
X.Y. Kong, et al., “Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells”, Disease Models & Mechanisms, vol. 7, 2014, pp. 351-362.
Kong, X.Y., Nesset, C.K., Damme, M., Loeberg, E.-M., Lübke, T., Maehlen, J., Andersson, K.B., Roos, N., Thoresen, G.H., Rustan, A.C., Kase, E.T., Eskild, W.: Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms. 7, 351-362 (2014).
Kong, Xiang Yi, Nesset, Cecilie K., Damme, Markus, Loeberg, Else-Marit, Lübke, Torben, Maehlen, Jan, Andersson, Kristin B., Roos, Norbert, Thoresen, G. Hege, Rustan, Arild C., Kase, Eili T., and 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”. Disease Models & Mechanisms 7.3 (2014): 351-362.
Main File(s)
Access Level
OA Open Access
Last Uploaded
2014-04-23 10:18:02

This data publication is cited in the following publications:
This publication cites the following data publications:

1 Citation in Europe PMC

Data provided by Europe PubMed Central.

Lack of the Lysosomal Membrane Protein, GLMP, in Mice Results in Metabolic Dysregulation in Liver.
Kong XY, Kase ET, Herskedal A, Schjalm C, Damme M, Nesset CK, Thoresen GH, Rustan AC, Eskild W., PLoS ONE 10(6), 2015
PMID: 26047317

81 References

Data provided by Europe PubMed Central.

Lhx2-/- mice develop liver fibrosis.
Wandzioch E, Kolterud A, Jacobsson M, Friedman SL, Carlsson L., Proc. Natl. Acad. Sci. U.S.A. 101(47), 2004
PMID: 15536133
Chronic liver disease is triggered by taurine transporter knockout in the mouse.
Warskulat U, Borsch E, Reinehr R, Heller-Stilb B, Monnighoff I, Buchczyk D, Donner M, Flogel U, Kappert G, Soboll S, Beer S, Pfeffer K, Marschall HU, Gabrielsen M, Amiry-Moghaddam M, Ottersen OP, Dienes HP, Haussinger D., FASEB J. 20(3), 2006
PMID: 16421246
Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice.
Weber A, Boger R, Vick B, Urbanik T, Haybaeck J, Zoller S, Teufel A, Krammer PH, Opferman JT, Galle PR, Schuchmann M, Heikenwalder M, Schulze-Bergkamen H., Hepatology 51(4), 2010
PMID: 20099303
Mouse models of liver fibrosis.
Weiler-Normann C, Herkel J, Lohse AW., Z Gastroenterol 45(1), 2007
PMID: 17236120
HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis.
White C, Yuan X, Schmidt PJ, Bresciani E, Samuel TK, Campagna D, Hall C, Bishop K, Calicchio ML, Lapierre A, Ward DM, Liu P, Fleming MD, Hamza I., Cell Metab. 17(2), 2013
PMID: 23395172
Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo.
Zhan SS, Jiang JX, Wu J, Halsted C, Friedman SL, Zern MA, Torok NJ., Hepatology 43(3), 2006
PMID: 16496318

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 24487409
PubMed | Europe PMC

Search this title in

Google Scholar