All Phenotypes Acot12<em1Holi> MGI Mouse

increased incidence of tumors by chemical induction ( J:335836 )

• following administration of DEN (N-nitrosodiethylamine) and CCl4 (carbon tetrachloride), incidence of liver tumors is increased to 100% after 5.5 weeks versus 40% in controls, with 100% of mice in both groups developing tumors after 11 weeks

• after 11 weeks of CCl4 administration, number of tumors per liver is increased by 50% and liver-to-body weight ratio is higher than in DEN/CCl4-treated wild-type controls

• accelerated liver tumor formation is associated with reduced Hippo signaling and increased yes-associated protein (YAP)-mediated transcriptional activity

• partial restoration of hepatic Acot12 expression using AAV-Acot12 inhibits hepatocarcinogenesis and YAP activation in DEN/CCl4-treated mice

increased hepatocellular carcinoma incidence ( J:335836 )

• male mice fed a NASH (non-alcoholic steatohepatitis) diet for 18 months to induce hepatocellular carcinoma show a 150% increase in liver tumor number and increased liver-to-body weight ratios relative to controls

• NASH-diet induced hepatocarcinogenesis is accelerated in the setting of hepatic glycerolipid accumulation and enhanced YAP activation, similar to the DEN/CCl4-induced model

increased tumor growth/size ( J:335836 )

• after 11 weeks of CCl4 administration, mice show a 300% increase in total liver tumor volume, a 40% increase in maximal tumor diameter, and a 200% increase in maximal tumor size while average number of Ki-67+ cells per field is higher than in DEN/CCl4-treated wild-type controls

• NASH diet-fed mice show 150%, 700%, 160% and 430% increases in liver tumor number, volume, maximal diameter, and maximal size, respectively

• partial restoration of hepatic Acot12 expression using AAV-Acot12 significantly decreases maximal tumor size in DEN/CCl4-treated mice

increased circulating cholesterol level ( J:335836 )

• DEN/CCl4-treated mice show a 52%, 59%, and 58% increase in plasma concentrations of total, free, and esterified cholesterol, respectively

abnormal ion homeostasis ( J:335836 )

• DEN/CCl4-treated mice show a 37% reduction in hepatic acetate concentrations in non-tumor liver tissue

• however, steady-state concentrations of acetyl-CoA in non-tumor liver tissue are normal

increased liver cholesterol level ( J:335836 )

• DEN/CCl4-treated mice show a 15% increase in total cholesterol concentration in non-tumor liver tissue

• however, concentrations of free and esterified cholesterol are normal in non-tumor liver tissue

abnormal phospholipid level ( J:335836 )

• DEN/CCl4-treated mice show a 52% increase in phospholipid concentration in liver tumor tissue but normal concentrations of phospholipids in non-tumor liver tissue

• in response to DEN/CCl4, mice show increased hepatic glycerolipid biosynthesis leading to 52% increase in concentrations of 16:0 LPA (lysophosphatidic acid), a trend towards increased concentrations of 18:0 LPA, and a significantly higher expression of its receptor, LPAR3, in tumor tissue

increased circulating phospholipid level ( J:335836 )

• DEN/CCl4-treated mice show a 31% increase in plasma phospholipid concentrations relative to controls

• NASH diet-fed mice show a 24% increase in plasma phospholipid concentrations relative to controls

increased liver triglyceride level ( J:335836 )

• DEN/CCl4-treated mice show a 66% increase in triglyceride (TG) concentration in non-tumor liver tissue and a 178% increase in TG concentration in tumor tissue

• however, plasma TG concentrations are normal