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FAT10 knock out mice livers fail to develop Mallory–Denk bodies in the DDC mouse model
- Source :
- Experimental and Molecular Pathology. 93:309-314
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Mallory–Denk bodies (MDBs) are aggresomes composed of undigested ubiqutinated short lived proteins which have accumulated because of a decrease in the rate of their degradation by the 26s proteasome. The decrease in the activity of the proteasome is due to a shift in the activity of the 26s proteasome to the immunoproteasome triggered by an increase in expression of the catalytic subunits of the immunoproteasome which replaces the catalytic subunits of the 26s proteasome. This switch in the type of proteasome in liver cells is triggered by the binding of IFNγ to the IFNγ sequence response element (ISRE) located on the FAT10 promoter. To determine if either FAT10 or IFNγ are essential for the formation of MDBs we fed both IFNγ and FAT10 knock out (KO) mice DDC added to the control diet for 10 weeks in order to induce MDBs. Mice fed the control diet and Wild type mice fed the DDC or control diet were compared. MDBs were located by immunofluorescent double stains using antibodies to ubiquitin to stain MDBs and FAT10 to localize the increased expression of FAT10 in MDB forming hepatocytes. We found that MDB formation occurred in the IFNγ KO mice but not in the FAT10 KO mice. Western blots showed an increase in the ubiquitin smears and decreases β 5 (chymotrypsin-like 26S proteasome subunit) in the Wild type mice fed DDC but not in the FAT10 KO mice fed DDC. To conclude, we have demonstrated that FAT10 is essential to the induction of MDB formation in the DDC fed mice.
- Subjects :
- Male
Proteasome Endopeptidase Complex
Clinical Biochemistry
Response element
Mallory Bodies
Response Elements
Article
Pathology and Forensic Medicine
Interferon-gamma
Mice
Species Specificity
Ubiquitin
medicine
Animals
Humans
Mallory body
Interferon gamma
Gene Silencing
Ubiquitins
Molecular Biology
Mice, Knockout
Mice, Inbred C3H
biology
Organ Size
Dicarbethoxydihydrocollidine
medicine.disease
Molecular biology
Blot
Disease Models, Animal
Aggresome
Liver
Proteasome
Knockout mouse
Hepatocytes
biology.protein
Chemical and Drug Induced Liver Injury
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 00144800
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Experimental and Molecular Pathology
- Accession number :
- edsair.doi.dedup.....584bab5ab1a55f396c96d2d6681ec690