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Experiment

Liver TG levels in Atp7btx-J mice
Summary Data Summary
Investigator Medici, Valentina
Description Hepatic methionine metabolism may play an essential role in regulating
methylation status and liver injury in Wilson’s disease (WD) through the
inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the
consequent accumulation of S-adenosylhomocysteine (SAH). We studied the
transcript levels of selected genes related to liver injury, levels of SAHH,
SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b), and global DNA
methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were
compared to those in control C3H mice, and in response to Cu chelation by
penicillamine (PCA) and dietary supplementation of the methyl donor betaine to
modulate inflammatory and methylation status. Transcript levels of selected
genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid
oxidation were down-regulated at baseline in tx-j mice, further down-regulated
in response to PCA, and showed little to no response to betaine. Hepatic Sahh
transcript and protein levels were reduced in tx-j mice with consequent increase
of SAH levels. Hepatic Cu accumulation was associated with inflammation, as
indicated by histopathology and elevated serum alanine aminotransferase (ALT)
and liver tumor necrosis factor alpha (Tnf-a) levels. Dnmt3b was downregulated
in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j
mice reduced Tnf-a and ALT levels, betaine treatment increased
S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments
restored global DNA methylation levels. Conclusion: Reduced hepatic Sahh
expression was associated with increased liver SAH levels in the tx-j model of
WD, with consequent global DNA hypomethylation. Increased global DNA methylation
was achieved by reducing inflammation by Cu chelation or by providing methyl
groups. We propose that increased SAH levels and inflammation affect widespread
epigenetic regulation of gene expression in WD. (HEPATOLOGY 2013;57:555-565)
Status Completed
Public Release 2/12/2015
Animal Age Measured In: week(s) post-natal (w)
Flags has-data-flaghas-doc-data-flagMetadataExperiment Description
Data Analysis
TypeCount
Animals13
Experimental Conditions1
Catalog Items1
Curation Info (# flags)2
Phenotype Assays1
Phenotype Measurements23
Histology Images0
Publications0
Documents1


Animals
Strain NameCommon NameFemalesMalesUnknown
C3
0
6
0
C3He-Atp7btx-J/J
0
7
0

Animals/Strains
Experimental Factors
 Categorical Values
Name / AbbreviationDescription

Experimental Factor: Experimental Group

 Control
This animal belongs to the control group for the experiment.
 Experiment
This animal belongs to experimental group that is homozygous for gene manipulations.
Experimental Factor (Units)
Experimental Group
Experimental Factor Values


Phenotype Assays Add / Edit


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