Phenotypes Associated with This Genotype

Genotype
MGI:2448162

• Allelic Composition: Acadl^tm1Uab/Acadl^tm1Uab
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Histopathology on Acadl^tm1Uab/Acadl⁺ and Acadl^tm1Uab/Acadl^tm1Uab mice

mortality/aging

premature death ( J:51660 )

• a small number of animals die suddenly between 2-14 weeks of age

prenatal lethality, incomplete penetrance ( J:51660 )

• partial embryonic lethality, lower than expected number of pups

cardiovascular system

abnormal heart morphology ( J:51660 , J:72193 )

• after an overnight fast, mutants develop microvesicular cardiac lipidosis (cardiac lesions) (J:51660)

• fasted mice display fatty change in hearts (J:72193)

cardiac fibrosis ( J:51660 )

• 10% of adult males have severe, multifocal myocardial fibrosis

homeostasis/metabolism

abnormal adaptive thermogenesis ( J:50729 )

• mutant mice tested were very sensitive to the cold, with rectal temperature dropping 10-15 degrees C within 2 hours of exposure to 4 degrees C

increased circulating carnitine level ( J:72193 )

• C10, C12 and C14 acylcarnitine esters are elevated

• concentration of total acylcarnitine metabolites is higher than in homozygous Acadvl^tm1Uab mutants or in wild-type mice

• C14:2 and C14:1 acylcarnitine esters are elevated in the blood

hypoglycemia ( J:51660 )

• fasted mutants have reduced mean serum glucose concentration, however concentrations are highly varied

abnormal lipid homeostasis ( J:72193 )

• fasted mice display fatty change in hearts

increased fatty acids level ( J:72193 )

• serum fatty acids C14:2 and C14:1 are elevated

• significant accumulation of liver fatty acids, with the highest absolute elevation of Myristate (C14) and the largest proportionate increase of C14:1 with respect to wild-type levels

increased circulating free fatty acids level ( J:51660 )

• fasted mutants show an elevation in serum FFA levels

increased unsaturated fatty acids level ( J:51660 )

• specific elevations in unsaturated fatty acids: docenedioic, tetradecenedioic, tetradecadienoic, oleic and linoleic acids

lipidosis ( J:51660 )

• lipid accumulation in the heart

dicarboxylic aciduria ( J:51660 , J:72193 )

• urine organic analysis of fasted mice shows excretion of high levels of adipic, octenedioic, decenedioic, and hydroxydecenedioic acids compared to wild-type, indicating dicarboxylic aciduria (J:51660)

• significantly elevated suberic acid (C8:0) and octenedioic acid (C8:1) in the urine of fasted, but not fed, mice compared to wild-type (J:72193)

abnormal enzyme/coenzyme activity ( J:51660 , J:72193 )

• cultured fibroblasts show a 28% reduction in ability to dehydrogenate palmitoyl-CoA compared to wild-type (J:51660)

• reduction in mitochondrial acyl-CoA dehydrogenase activity toward octanoyl-CaA, palmitoyl-CoA, 2,6-dimethlylheptanoyl-CoA, and Oleoyl-CoA in liver, heart and skeletal muscle (J:72193)

liver/biliary system

hepatic steatosis ( J:51660 )

macrovesicular hepatic steatosis ( J:51660 , J:72193 )

• after an overnight fast, mutants develop severe and diffuse macrovesicular hepatic steatosis (J:51660)

• fasted mice display severe hepatosteatosis with predominantly large, uniformly distributed droplets throughout the livers (J:72193)

microvesicular hepatic steatosis ( J:51660 )

• after an overnight fast, mutants develop severe and diffuse microvesicular hepatic steatosis

abnormal bile composition ( J:51660 )

• bile of fasted mutants contains extremely high concentrations of C14:1 and C14:2 acylcarnitines

reproductive system

decreased litter size ( J:51660 , J:72193 )

• on average 6.7 pups per litter compared to 8.5 in wild-type (J:72193)

renal/urinary system

dicarboxylic aciduria ( J:51660 , J:72193 )

• urine organic analysis of fasted mice shows excretion of high levels of adipic, octenedioic, decenedioic, and hydroxydecenedioic acids compared to wild-type, indicating dicarboxylic aciduria (J:51660)

• significantly elevated suberic acid (C8:0) and octenedioic acid (C8:1) in the urine of fasted, but not fed, mice compared to wild-type (J:72193)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
very long chain acyl-CoA dehydrogenase deficiency		DOID:0080155	OMIM:201475	J:51660