All Phenotypes Selenov<em1Xgl> MGI Mouse

decreased glutathione level ( J:321026 )

• diquat (DQ)- and N-acetyl-para-aminophenol (APAP)-treated primary hepatocytes show 26%-87% lower glutathione (GSH) contents than treatment-matched wild-type hepatocytes

increased circulating alanine transaminase level ( J:321026 )

• DQ- and APAP-injected males show 60% and 87% higher serum alanine aminotransferase (ALT) activities, respectively, than treatment-matched wild-type controls

decreased superoxide dismutase level ( J:321026 )

• primary hepatocytes show 36% and 28% lower superoxide dismutase (SOD) activities after treatment with 1 mM APAP and 0.25 mM DQ, respectively

increased physiological sensitivity to xenobiotic ( J:321026 )

• 8-wk old males fed a selenium-adequate diet and i.p. injected with diquat (DQ, 12.5 mg/kg) show 60% and 46% higher serum ALT activities and hepatic malondialdehyde (MDA) contents, respectively, and 43% lower hepatic total anti-oxidizing-capability (T-AOC) than DQ-injected wild-type controls

• males i.p. injected with N-acetyl-para-aminophenol (APAP, 300 mg/kg) show 87%, 35% and 17% higher levels of serum ALT activities, hepatic MDA, and hepatic protein carbonyl contents, respectively, and 40% lower hepatic T-AOC than APAP-injected wild-type controls

• APAP-injected males show stronger formation of 3-nitrotyrosine (3-NT), a unique biomarker for reactive nitrogen species (RNS)-mediated hepatotoxicity, in the liver than APAP-injected wild-type controls

• although DQ injection induces formation of 3-NT over saline-injected controls, the genotype difference is less pronounced relative to the APAP injection

increased hepatocyte apoptosis ( J:321026 )

• saline-injected males have 3.4-fold greater amounts of hepatic caspase-9 proteins than saline-injected wild-type controls

• overall, DQ-injected males show 1.6-fold and 33% greater amounts of hepatic FAK and caspase-9 proteins, respectively, than DQ-injected wild-type controls

• APAP-injected males show 55% greater amounts of hepatic FAK protein than APAP-injected wild-type controls, but similar amounts of hepatic caspase-9 protein between genotypes

hepatic necrosis ( J:321026 )

• both DQ- and APAP-injected males exhibit more severe hepatic necrosis in the central lobular areas than treatment-matched wild-type controls

increased cellular sensitivity to oxidative stress ( J:321026 )

• DQ- and APAP-treated primary hepatocytes show dose-dependent decreases in cell viability, leading to 8%-38% lower viability than treatment-matched wild-type hepatocytes

increased hepatocyte apoptosis ( J:321026 )

• saline-injected males have 3.4-fold greater amounts of hepatic caspase-9 proteins than saline-injected wild-type controls

• overall, DQ-injected males show 1.6-fold and 33% greater amounts of hepatic FAK and caspase-9 proteins, respectively, than DQ-injected wild-type controls

• APAP-injected males show 55% greater amounts of hepatic FAK protein than APAP-injected wild-type controls, but similar amounts of hepatic caspase-9 protein between genotypes

abnormal cellular respiration ( J:321026 )

• APAP-treated primary hepatocytes show lower basal respiration (29-35%), non-mitochondrial respiration (40-73%), and ATP production (34-46%) than APAP-treated wild-type hepatocytes at all three tested doses

• maximal respiration is 19-31% lower after 0- and 6 mM APAP exposure, respectively, while spare respiration is 26% lower after 1 mM APAP exposure

increased endoplasmic reticulum stress ( J:321026 )

• saline-injected males have 2.9-fold greater amounts of hepatic BIP proteins than saline-injected wild-type controls

• overall, DQ-injected males show 81% and 1.2-fold greater amounts of hepatic BIP and CHOP proteins, respectively, than DQ-injected wild-type controls

• APAP-injected males show 24% greater amounts of hepatic BIP proteins than APAP-injected wild-type controls, with no alteration in hepatic CHOP protein production in either genotype

oxidative stress ( J:321026 )

• DQ-injected males show 46% higher hepatic malondialdehyde (MDA) contents and 43% lower hepatic total anti-oxidizing-capability (T-AOC) than DQ-injected wild-type controls

• APAP-injected males show 35% and 17% higher levels of hepatic MDA and protein carbonyl contents, respectively, and 40% lower hepatic T-AOC than APAP-injected wild-type controls

• isolated primary hepatocytes show 63%-83% lower levels of T-AOC than wild-type hepatocytes after treatment with various doses of APAP and DQ

• DQ- and APAP-treated primary hepatocytes show 26%-87% lower glutathione (GSH) contents and 33%-72% lower ratios of GSH to glutathione disulfide (GSH/GSSG) than treatment-matched wild-type hepatocytes

• moreover, mRNA levels of antioxidant-related genes (Gcs, Cat, Gpx3 and Sod) are 29%-90% lower at the baseline and 21%-92% lower after treatment with APAP or DQ

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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