title: Age-dependent development of liver fibrosis in Glmp (gt/gt) mice.
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.
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Cecilie K
authors.initials: CK
authors.lastname: Nesset
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway ; Research Institute for Internal Medicine, University of Oslo, Oslo, Norway ; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway ; K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Xiang Yi
authors.initials: XY
authors.lastname: Kong
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-Universität Kiel, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Damme
authors.affiliation: Department of Immunology, University of Oslo, Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Schjalm
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Norbert
authors.initials: N
authors.lastname: Roos
authors.affiliation: Department of Pathology, Oslo University Hospital Ullevaal, Oslo, Norway.
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Winnie
authors.initials: W
authors.lastname: Eskild
keywords: Inflammation; Liver fibrosis; Liver tumors; Oval cells; Transgenic mouse model