All Phenotypes Selenov<em1Xgl> MGI Mouse

homeostasis/metabolism phenotype ( J:311586 )

N	• 4-month-old males fed a normal fat (NF) diet show no significant changes in serum concentrations of testosterone, or testis gene expression and protein production involved in testosterone biosynthesis

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 leptin level ( J:311586 )

• by 6 months (endpoint), HF-fed males show 46% higher serum leptin concentrations than HF-fed wild-type controls

increased circulating cholesterol level ( J:311586 )

• by 6 months (endpoint), NF- and HF-fed males show 50% and 16% higher serum total cholesterol concentrations, respectively, than diet-matched wild-type controls

increased circulating chemokine level ( J:311586 )

• by 6 months (endpoint), NF- and HF-fed males show 107% and 37% higher serum CCL2 (C-C motif chemokine ligand 2; aka MCP-1) concentrations, respectively, than diet-matched wild-type controls

decreased circulating interleukin-6 level ( J:311586 )

• by 6 months (endpoint), males fed either NF or HF diet exhibit decreased serum IL-6 concentrations by 10-12%

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 body surface temperature ( J:311586 )

• both NF- and HF-fed males exhibit lower body surface temperature than diet-matched wild-type controls, esp. in the interscapular region

decreased core body temperature ( J:311586 )

• males fed an HF-diet at an ambient temperature of 22 degrees Celsius exhibit an average core (rectal) body temperature that is 0.6 degrees lower than that in HF-fed wild-type controls

• after acute cold exposure (4 degrees Celsius for 1 h), NF-fed males show an average core temperature that is 0.2 degrees lower than that in NF-fed wild-type controls

decreased energy expenditure ( J:311586 )

• total energy expenditure (EE) is decreased by 14-23% in NF-fed males and by 16-22% in HF-fed males

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

decreased carbon dioxide production ( J:311586 )

• total VCO2 production is decreased by 16% or 14% in NF-fed males and by 33% or 32% in HF-fed males

decreased oxygen consumption ( J:311586 )

• total VO2 consumption is decreased by 14-21% in NF-fed males and by 15-20% in HF-fed males

• primary preadipocytes isolated from 4-month-old males fed the NF diet show a sharp decline in cellular total respiration ability with a 66% decrease in the maximum oxygen consumption rate (OCR)

abnormal respiratory quotient ( J:311586 )

• HF-fed males show a shift in the respiratory quotient (RQ) from 0.91 (carbohydrate-based energy) to 0.76 (lipid-based energy)

increased lipogenesis ( J:311586 )

• extra fat accumulation is partly mediated by upregulation of genes and proteins involved in lipogenesis (Acc, Fas, Dgat, and Lpl; up by 40%-1.1-fold) in adipose tissues

impaired lipolysis ( J:311586 )

• extra fat accumulation is partly mediated by downregulation of lipolysis genes (Atgl, Hsl, Ces1d, and Cpt1a; down by 36-89%) in adipose tissues

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

oligozoospermia ( J:311586 )

• 4-month-old males fed a normal-fat (NF) diet show a small but significant reduction in average sperm count relative to wild-type controls

• however, sperm morphology and vitality, sperm motility, testicular histology, breeding and male fertility are largely normal

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

increased body fat mass ( J:311586 )

• both NF- and HF-fed males show increased total body fat mass, with 54% more total fat than diet-matched wild-type controls

• however, total dietary digestible energy intake is unaffected in mice fed either diet

increased body weight ( J:311586 )

• male body weights are normal at 4 months of age but 8% and 12% higher than those of wild-type controls at 5 and 6 months of age, respectively

• after 20 weeks of age, male mice are heavier, whether fed a normal-fat (NF) or a high-fat diet (HF) diet; by 6 months (endpoint), NF-fed males are 16% heavier while HF-fed males are 19% heavier than diet-matched wild-type controls

• moderate increase in body weight is mainly due to elevated fat mass accumulation in various adipose tissues

increased body fat mass ( J:311586 )

• both NF- and HF-fed males show increased total body fat mass, with 54% more total fat than diet-matched wild-type controls

• however, total dietary digestible energy intake is unaffected in mice fed either diet

increased brown adipose tissue mass ( J:311586 )

• by 6 months (endpoint), NF-fed males have gained 31% more BAT than NF-fed wild-type controls

whitened brown adipose tissue morphology ( J:311586 )

• H&E staining of brown adipose tissue (BAT) shows loss of characteristic morphology and increased whitening of brown adipocytes

increased white fat cell lipid droplet size ( J:311586 )

• males fed either NF or HF diet exhibit enlarged lipid droplets in epididymal WAT (EWAT)

increased white fat cell size ( J:311586 )

• males fed either NF or HF diet exhibit adipocyte hypertrophy and enlarged lipid droplets in epididymal WAT (EWAT)

increased epididymal fat pad weight ( J:311586 )

• by 6 months (endpoint), NF-fed males have gained 1.4-fold more epididymal WAT (EWAT) than NF-fed wild-type controls, while HF-fed males have gained 25% more EWAT than HF-fed wild-type controls

increased inguinal fat pad weight ( J:311586 )

• by 6 months (endpoint), NF-fed males have gained 1.5-fold more inguinal WAT than NF-fed wild-type controls

increased mesenteric fat pad weight ( J:311586 )

• by 6 months (endpoint), NF-fed males have gained 99% more mesenteric WAT than NF-fed wild-type controls

increased renal fat pad weight ( J:311586 )

• by 6 months (endpoint), NF-fed males have gained 2.0-fold more perinephric WAT than NF-fed wild-type controls, while HF-fed males have gained 1.1-fold more than perinephric WAT than HF-fed wild-type controls

abnormal brown adipose tissue physiology ( J:311586 )

• by 6 months, levels of O-GlcNAc transferase (OGT) protein in BAT are reduced by 32-50% in NF-fed males and by 46-60% in HF-fed males

• moreover, global O-GlcNAcylated protein levels in BAT are decreased by 45-56% in NF-fed males and by 36-47% in HF-fed males

abnormal brown adipose tissue thermogenesis ( J:311586 )

• males fed either diet (NF or HF) show a 22-41% decrease in the mRNA levels of thermogenesis-related genes (Cpt1a, Prdm16, Pparg, and Ppargc1a) in BAT; moreover, protein levels of CPT1A and UCP1 are reduced by 34-52% in BAT

abnormal white adipose tissue physiology ( J:311586 )

• 4-month-old males fed the NF diet show a ~40% decrease in total O-GlcNAc transferase (OGT) activity in WAT

• by 6 months, levels of OGT protein in WAT are reduced by 15-29% in NF-fed males but increased by 30-55% in HF-fed males

• moreover, global O-GlcNAcylated protein levels in WAT are decreased by 10-21% in NF-fed males and by 14-24% in HF-fed males