Expression of an epidermal keratin protein in liver of transgenic mice causes structural and functional abnormalities.
Open Access
- 1 January 1995
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 128 (1), 157-169
- https://doi.org/10.1083/jcb.128.1.157
Abstract
To examine the role of keratin intermediate filament proteins in cell structure and function, transgenic mice were isolated that express a modified form of the human K14 keratin protein in liver hepatocytes. A modified K14 cDNA (K14.P) sequence was linked downstream of the mouse transthyretin (TTR) gene promoter and enhancer elements to achieve targeted expression in hepatocytes. Hepatocytes expressing high levels of the transgene were found to have abnormal keratin filament networks as detected by indirect immunofluorescence using an antibody specific for the transgene product. Light and electron microscopic level histological analysis of isolated liver tissue showed in many cases degenerative changes that included inflammatory infiltration, ballooning degeneration, an increase in fat containing vacuoles, and glycogen accumulation. These changes were most evident in older mice over four months of age. No indication of typical Mallory body structures were identified at either the light or electron microscopic level. To evaluate secretory function in transgenic livers, bile acid secretion rates were measured in isolated perfused liver and found to be approximately twofold lower than aged-matched controls. These findings indicate that expression of an abnormal keratin in liver epithelial cells in the in vivo setting can alter the structure and function of a tissue and suggest a role of the keratin network in cellular secretion.Keywords
This publication has 51 references indexed in Scilit:
- INTERMEDIATE FILAMENTS: Structure, Dynamics, Function and DiseaseAnnual Review of Biochemistry, 1994
- Ectopic synthesis of epidermal cytokeratins in pancreatic islet cells of transgenic mice interferes with cytoskeletal order and insulin production.The Journal of cell biology, 1993
- Intermediate filament molecular biologyCurrent Opinion in Cell Biology, 1992
- Polarized and functional epithelia can form after the targeted inactivation of both mouse keratin 8 alleles.The Journal of cell biology, 1991
- Role of Cytokeratin Intermediate Filaments in Transhepatic Transport and Canalicular SecretionHepatology, 1990
- Synthesis and fate of keratins 8 and 18 in nonepithelial cells transfected with cDNA*1Experimental Cell Research, 1988
- Patterns of Expression and Organization of Cytokeratin Intermediate FilamentsAnnals of the New York Academy of Sciences, 1985
- Immunological and biochemical characterization of the keratin‐related component of Mallory bodies: A pathological pattern of hepatocytic cytokeratinsLiver International, 1982
- Two distinct classes of keratin genes and their evolutionary significanceCell, 1981
- Detection of specific sequences among DNA fragments separated by gel electrophoresisJournal of Molecular Biology, 1975