All Phenotypes Cyp27a1<tm1Elt> MGI Mouse

decreased lung cholesterol level ( J:115373 )

• slight reduction of cholesterol concentration in the lungs

homeostasis/metabolism phenotype ( J:115373 )

N	• males show normal plasma levels of glucose, corticosterone, ACTH, and testosterone at 3-4 months of age

abnormal feces lipid level ( J:115373 )

• 2.5-fold increase in fecal neutral sterol excretion relative to wild-type controls

decreased intestinal cholesterol absorption ( J:115373 )

• severe reduction in intestinal cholesterol absorption (4% from 54% in wild-type controls)

• intestinal cholesterol absorption is restored to normal levels by cholic acid feeding

abnormal circulating cholesterol level ( J:48127 )

• concentration of circulating 7-alpha hydroxycholesterol is 4-10 fold higher in null mice

increased circulating triglyceride level ( J:115373 )

• 2-fold increase in plasma total triacylglycerol levels on a conventional low fat, low cholesterol diet

• plasma triacylglycerol levels are essentially normalized by cholic acid feeding

increased circulating VLDL triglyceride level ( J:115373 )

• marked increase in plasma triacylglycerol levels is confined to the VLDL fraction

abnormal bile salt homeostasis ( J:115373 )

• 5-fold increase in cholesterol 7alpha-hydroxylase activity relative to wild-type controls

decreased bile salt level ( J:115373 )

• bile acid pool size is only 27% of that in wild-type controls

• total bile acid synthesis is about 47% of that in wild-type controls, as measured by the rate of fecal bile acid excretion

decreased feces bile salt level ( J:115373 )

• fecal bile acid excretion is about 47% of that in wild-type controls

decreased lung cholesterol level ( J:115373 )

• slight reduction of cholesterol concentration in the lungs

increased fatty acids level ( J:115373 )

• 70% increase in hepatic fatty acid synthesis relative to wild-type controls

• marked shift in hepatic fatty acid composition with a ~70% increase in the proportion of oleic (18:1) to stearic acid (18:0)

• hepatic fatty acid synthesis is essentially normalized by cholic acid feeding

• no change in the rates of fatty acid synthesis in adrenal gland, lung, or small intestine tissue

increased sterol level ( J:115373 )

• significant increase of two non-cholesterol sterols, identified as the two forms of lathosterol, in the adrenal glands, not detected in wild-type adrenals

• trace amounts of the two lathosterol forms (~4% of total tissue sterol content) in the lungs, unlike in wild-type controls

increased cholesterol level ( J:48127 , J:115373 )

• amount of 7 alpha-hydroxycholesterol in liver, kidney and brain is markedly higher in null animals (J:48127)

• 48% increase of cholesterol concentration in the adrenal glands relative to wild-type controls (J:115373)

• marked increase in cholesterol synthesis in the liver and adrenal gland (4-fold), lung (2.9-fold), spleen (2.4-fold), and small intestine (1.8-fold) (J:115373)

• 2.5-fold increase in whole animal cholesterol synthesis relative to wild-type controls, with ~90% attributed to hepatic synthesis (J:115373)

• cholic acid feeding reduces sterol synthesis in the liver and adrenal gland to values significantly below those seen in wild-type mice fed the basal diet alone (J:115373)

increased circulating cholesterol level ( J:115373 )

• 30% increase in plasma total cholesterols level on a conventional low fat, low cholesterol diet

increased circulating VLDL cholesterol level ( J:115373 )

• marked increase in plasma cholesterol levels is confined to the VLDL fraction

increased vitamin D level ( J:48127 )

• levels of 25-hydroxyvitamin D are slightly higher in nulls than in wild-type

increased liver triglyceride level ( J:115373 )

• 2.4-fold increase in hepatic triacylglycerol levels relative to wild-type controls

• hepatic triacylglycerol levels are essentially normalized by cholic acid feeding

enlarged liver ( J:115373 )

• significant hepatomegaly at 3-4 months of age

• hepatomegaly is almost fully reversed by cholic acid or chenodeoxycholic acid feeding

increased liver weight ( J:115373 )

• 40% increase in liver weight relative to wild-type controls

increased liver triglyceride level ( J:115373 )

• 2.4-fold increase in hepatic triacylglycerol levels relative to wild-type controls

• hepatic triacylglycerol levels are essentially normalized by cholic acid feeding

abnormal bile composition ( J:48127 , J:115373 )

• concentration of bile acids in hydrolyzed bile sample from knockout mice is 0.9 mg/ml compared to about 8 mg/ml in a wild-type sample (J:48127)

• molar ratio of cholesterol in gallbladder bile is double that in wild-type controls, due to a significant reduction in bile acid and phospholipid levels while biliary cholesterol concentration remains normal (J:115373)

• bile acid concentration in gallbladder bile is only 37% of that in wild-type controls (J:115373)

• however, bile acid species are similar to those in wild-type controls, with cholic acid predominating in both cases (J:115373)

enlarged adrenocortical cells ( J:115373 )

• upon histology, adrenomegaly reflects cortical cell hypertrophy

increased adrenal gland weight ( J:115373 )

• 45% increase in adrenal gland weight relative to wild-type controls

enlarged adrenal glands ( J:115373 )

• significantly enlarged adrenal glands at 3-4 months of age

• adrenomegaly is NOT reversed by cholic acid feeding

abnormal feces composition ( J:115373 )