All Phenotypes Sult2a8<tm1Sstl> MGI Mouse

homeostasis/metabolism phenotype ( J:327124 , J:344979 )

N

• mice show normal hepatic bile acid metabolism, showing no difference in tissue contents of all the 7alpha-hydroxyl bile acids (CA, T-CA, CDCA, T-CDCA, G-CDCA, alphaMCA and T-alpha-MCA) (J:327124)

• in the fed and fasted state, mice show normal plasma beta-hydroxybutyrate levels, indicating no effect on ketone production, show normal plasma glucose, insulin and leptin levels, indicating no effect on glucose metabolism, and have normal plasma triglycerides, plasma glycerol and serum free fatty acids indicating no effect on triglyceride metabolism (J:344979)

decreased circulating cholesterol level ( J:327124 , J:344979 )

• fasted, but not fed, males exhibit an approximate 50% reduction in plasma cholesterol levels (J:344979)

• fasted males, but not females, show a reduction of plasma cholesterol levels compared to fasted wild-type mice (J:327124)

• however, fasting plasma levels of triglyceride, glycerol, and free fatty acids are unaffected and fasting-induced increase in plasma beta-hydroxybutyrate and decrease in the plasma glucose level or the low blood glucose-induced suppression of insulin and leptin secretions compared to wild-type fasted mice are unaffected (J:327124)

abnormal enzyme/coenzyme level ( J:327124 )

• males show an approximate 50% decrease in sulfonating enzyme activities towards the 7alpha-hydroxyl bile acid substrates

• however, no differences in hepatic sulfotransferase activities are seen in females towards all substrates tested

liver/biliary system phenotype ( J:327124 , J:344979 )

N	• mice exhibit normal gross liver structure and histology and fasting has no effects on liver histology (J:327124) • fed mice have normal liver histology and fasting has no effect on liver histology (J:344979)

abnormal bile composition ( J:327124 , J:344979 )

• males exhibit an increase in hepatic tauro-cholic acid (T-CA) levels during fasting (J:327124)

• bile acid pools in liver, bile, plasma and urine are unaffected and no changes in most hepatic bile acid pools are seen in the fed state, indicating that bile acid metabolism is intact (J:344979)

• in the fed state, females show a decrease in the level of hepatic glycol-chenodeoxycholic acid (G-CDCA) (J:344979)

• while wild-type males show an increase in hepatic tauro-chenodeoxycholic acid (T-CDCA) levels upon fasting, mutant males show only an increase in hepatic tauro-conjugated cholic acid (T-CA) levels upon fasting (J:344979)

• while wild-type fasted females show an increase in hepatic cholic acid 7-sulfate (CA-S), T-CA, T-CDCA, G-CDCA, and tauro-alpha-muricholic acid (T-alpha-MCA) levels upon fasting, mutant females only show an increase in hepatic chenodeoxycholic acid (CDCA) and glycolchenodeoxycholic acid (G-CDCA) levels upon fasting (J:344979)

• fed females show lower levels of biliary CA-S and G-CDCA (J:344979)

• fasted females mice show altered biliary bile acid pools, with increases in cholic acid (CA), CA-S, T-CA, T-CDCA, and alpha-MCA levels compared to fed females (J:344979)

• while fasted wild-type males show an increase in biliary T-CDCA level, this increase is not seen in mutant fasted males (J:344979)

• levels of plasma CA-S in fed males and fed females is lower than in wild-type fed males and females (J:344979)

• a very slight increase of plasma G-CDCA is seen in fed males, but not fed females (J:344979)

• while an increase of plasma alpha-MCA level is seen in wild-type females following fasting, this increase is not seen in fasted mutant females and fasting has no significant effects on all other plasma bile acids (J:344979)

• urinary T-CA levels in fed males are lower than in fed wild-type males, however T-CA is only a minor proportion of total bile acids in urine (J:344979)

• the decrease in urinary T-CA and G-CDCA that is seen in males following fasting in wild-type mice is not seen in mutant males and fasting has no effects in the levels of the other urinary bile acid pools (J:344979)

abnormal liver morphology ( J:327124 )

• males exhibit an increase in hepatic tauro-cholic acid (T-CA) levels during fasting

• however, levels of CA, CA-S, and T-alpha-MCA are unchanged during fasting