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Fibrogenesis & Tissue Repair
Published in: Fibrogenesis & Tissue Repair 1/2016

Open Access 01-12-2016 | Research

Age-dependent development of liver fibrosis in Glmp gt/gt mice

Authors: Cecilie K. Nesset, Xiang Yi Kong, Markus Damme, Camilla Schjalm, Norbert Roos, Else Marit Løberg, Winnie Eskild

Published in: Fibrogenesis & Tissue Repair | Issue 1/2016

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Abstract

Background

Mice lacking glycosylated lysosomal membrane protein (Glmp gt/gt mice) have liver fibrosis as the predominant phenotype due to chronic liver injury. The Glmp gt/gt mice grow and reproduce at the same rate as their wild-type siblings. Life expectancy is around 18 months.

Methods

Wild-type and Glmp gt/gt mice were studied between 1 week and 18 months of age. Livers were analyzed using histological, immunohistochemical, biochemical, and qPCR analyses.

Results

It was shown that Glmp gt/gt mice were not born with liver injury; however, it appeared shortly after birth as indicated by excess collagen expression, deposition of fibrous collagen in the periportal areas, and increased levels of hydroxyproline in Glmp gt/gt liver. Liver functional tests indicated a chronic, mild liver injury. Markers of inflammation, fibrosis, apoptosis, and modulation of extracellular matrix increased from an early age, peaking around 4 months of age and followed by attenuation of these signals. To compensate for loss of hepatocytes, the oval cell compartment was activated, with the highest activity of the oval cells detected at 3 months of age, suggesting insufficient hepatocyte proliferation in Glmp gt/gt mice around this age. Although constant proliferation of hepatocytes and oval cells maintained adequate hepatic function in Glmp gt/gt mice, it also resulted in a higher frequency of liver tumors in older animals.

Conclusions

The Glmp gt/gt mouse is proposed as a model for slowly progressing liver fibrosis and possibly as a model for a yet undescribed human lysosomal disorder.
Appendix
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Metadata
Title
Age-dependent development of liver fibrosis in Glmp gt/gt mice
Authors
Cecilie K. Nesset
Xiang Yi Kong
Markus Damme
Camilla Schjalm
Norbert Roos
Else Marit Løberg
Winnie Eskild
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Fibrogenesis & Tissue Repair / Issue 1/2016
Electronic ISSN: 1755-1536
DOI
https://doi.org/10.1186/s13069-016-0042-4

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