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histopathologic examination of one group of mutant and MCAD+/+ control mice after a 24-h fast demonstrated diffuse microvesicular and macrovesicular hepatic steatosis in 6–8-wk-old MCAD−/− mice whereas MCAD+/+ mice had no histologic changes (Figure 5A and 5B). In another group of 4-wk-old MCAD+/+ and MCAD−/− mice fasted for 24-h, there were minimal to no abnormalities in all organs evaluated. Only the older MCAD−/− mice, therefore, demonstrated hepatic steatosis. In addition, we found sporadic cardiac lesions in multiple MCAD−/− mice.\nFigure 5 Histopathology of MCAD+/+ and MCAD−/− Mice\n(A) MCAD+/+ mice had no evidence of hepatic steatosis following a 24-h fast. Liver section with Oil-Red O stain.\n(B) Hepatosteatosis in MCAD−/− mouse following a 24-h fast. Oil-Red O stained liver sections revealed severe and diffuse microvesicular and macrovesicular hepatic steatosis in MCAD−/− mice.\n(C and D) Diffuse cardiomyopathy with chronic active multifocal myocyte degeneration and necrosis in MCAD−/− mice. In one example, an MCAD−/− mouse had diffuse cardiomyopathy with chronic active multifocal myocyte degeneration and necrosis (Figure 5C and 5D). Changes in degenerating myocytes included swelling, pale staining, and, in portions of the sarcoplasm, replacement of myofibrils with finely granular eosinophilic material. Nuclei of affected myocytes were large, pale, and vesicular and had prominent nucleoli. In the most severely affected areas, there was loss of myocytes accompanied by fibrosis. In the wall of the aorta at the base of the heart there was multifocal degeneration of the elastic tissue, accompanied by multifocal collections of globular translucent yellow-brown pigment interpreted to be ceroid/lipofuscin. Similar deposits were scattered within adjacent adipose tissue."}

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},{"id":"T3625","span":{"begin":205,"end":209},"obj":"GO_PR_EXT:medium_chain_acyl_CoA_dehydrogenase"},{"id":"T3624","span":{"begin":173,"end":180},"obj":"UBERON:0002107"},{"id":"T3623","span":{"begin":163,"end":172},"obj":"GO:0031982"},{"id":"T3622","span":{"begin":144,"end":153},"obj":"GO:0031982"},{"id":"T3621","span":{"begin":95,"end":99},"obj":"NCBITaxon:10088"},{"id":"T3620","span":{"begin":85,"end":86},"obj":"SO_EXT:normal_or_wild_type_or_present"},{"id":"T3619","span":{"begin":83,"end":84},"obj":"SO_EXT:normal_or_wild_type_or_present"},{"id":"T3618","span":{"begin":79,"end":83},"obj":"GO_PR_EXT:medium_chain_acyl_CoA_dehydrogenase"},{"id":"T3617","span":{"begin":68,"end":74},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T3668","span":{"begin":1575,"end":1580},"obj":"UBERON:0000948"},{"id":"T3667","span":{"begin":1550,"end":1555},"obj":"UBERON:0004663"},{"id":"T3666","span":{"begin":1538,"end":1545},"obj":"_FRAGMENT"},{"id":"T3665","span":{"begin":1497,"end":1505},"obj":"CL:0000187"},{"id":"T3664","span":{"begin":1432,"end":1440},"obj":"GO:0005730"},{"id":"T3663","span":{"begin":1404,"end":1413},"obj":"GO:0031982"},{"id":"T3662","span":{"begin":1373,"end":1381},"obj":"CL:0000187"},{"id":"T3661","span":{"begin":1354,"end":1360},"obj":"GO:0005634"},{"id":"T3660","span":{"begin":1331,"end":1343},"obj":"CL:0000771"},{"id":"T3659","span":{"begin":1299,"end":1309},"obj":"GO:0030016"},{"id":"T3658","span":{"begin":1272,"end":1282},"obj":"GO:0016528"},{"id":"T3657","span":{"begin":1205,"end":1213},"obj":"CL:0000187"},{"id":"T3656","span":{"begin":1152,"end":1160},"obj":"GO_PATO_EXT:necrosis"},{"id":"T3655","span":{"begin":1127,"end":1134},"obj":"CL:0000187"},{"id":"T3654","span":{"begin":1063,"end":1068},"obj":"NCBITaxon:10088"},{"id":"T3653","span":{"begin":1061,"end":1062},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T3652","span":{"begin":1059,"end":1060},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T3651","span":{"begin":1055,"end":1059},"obj":"GO_PR_EXT:medium_chain_acyl_CoA_dehydrogenase"}],"relations":[{"id":"R2321","pred":"_lexicallyChainedTo","subj":"T3667","obj":"T3666"}],"text":"Histopathology\nComplete histopathologic examination of one group of mutant and MCAD+/+ control mice after a 24-h fast demonstrated diffuse microvesicular and macrovesicular hepatic steatosis in 6–8-wk-old MCAD−/− mice whereas MCAD+/+ mice had no histologic changes (Figure 5A and 5B). In another group of 4-wk-old MCAD+/+ and MCAD−/− mice fasted for 24-h, there were minimal to no abnormalities in all organs evaluated. Only the older MCAD−/− mice, therefore, demonstrated hepatic steatosis. In addition, we found sporadic cardiac lesions in multiple MCAD−/− mice.\nFigure 5 Histopathology of MCAD+/+ and MCAD−/− Mice\n(A) MCAD+/+ mice had no evidence of hepatic steatosis following a 24-h fast. Liver section with Oil-Red O stain.\n(B) Hepatosteatosis in MCAD−/− mouse following a 24-h fast. Oil-Red O stained liver sections revealed severe and diffuse microvesicular and macrovesicular hepatic steatosis in MCAD−/− mice.\n(C and D) Diffuse cardiomyopathy with chronic active multifocal myocyte degeneration and necrosis in MCAD−/− mice. In one example, an MCAD−/− mouse had diffuse cardiomyopathy with chronic active multifocal myocyte degeneration and necrosis (Figure 5C and 5D). Changes in degenerating myocytes included swelling, pale staining, and, in portions of the sarcoplasm, replacement of myofibrils with finely granular eosinophilic material. Nuclei of affected myocytes were large, pale, and vesicular and had prominent nucleoli. In the most severely affected areas, there was loss of myocytes accompanied by fibrosis. In the wall of the aorta at the base of the heart there was multifocal degeneration of the elastic tissue, accompanied by multifocal collections of globular translucent yellow-brown pigment interpreted to be ceroid/lipofuscin. Similar deposits were scattered within adjacent adipose tissue."}