Mouse Genome Informatics
hm1
    Acadltm1Uab/Acadltm1Uab
involves: 129S6/SvEvTac * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Histopathology on Acadltm1Uab/Acadl+ and Acadltm1Uab/Acadltm1Uab mice

mortality/aging
• a small number of animals die suddenly between 2-14 weeks of age
• partial embryonic lethality, lower than expected number of pups

cardiovascular system
• after an overnight fast, mutants develop microvesicular cardiac lipidosis (cardiac lesions) (J:51660)
• fasted mice display fatty change in hearts (J:72193)
• 10% of adult males have severe, multifocal myocardial fibrosis

homeostasis/metabolism
• 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
• C10, C12 and C14 acylcarnitine esters are elevated
• concentration of total acylcarnitine metabolites is higher than in homozygous Acadvltm1Uab mutants or in wild-type mice
• C14:2 and C14:1 acylcarnitine esters are elevated in the blood
• fasted mutants have reduced mean serum glucose concentration, however concentrations are highly varied
• fasted mice display fatty change in hearts
• 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
• fasted mutants show an elevation in serum FFA levels
• specific elevations in unsaturated fatty acids: docenedioic, tetradecenedioic, tetradecadienoic, oleic and linoleic acids
• lipid accumulation in the heart
• 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)
• 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
• after an overnight fast, mutants develop severe and diffuse micro- and macrovesicular hepatic steatosis (J:51660)
• fasted mice display severe hepatosteatosis with predominantly large, uniformly distributed droplets throughout the livers (J:72193)
• bile of fasted mutants contains extremely high concentrations of C14:1 and C14:2 acylcarnitines

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

renal/urinary system
• 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 Genome Informatics
ht2
    Acadltm1Uab/Acadl+
involves: 129S6/SvEvTac * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• incomplete penetrance

reproductive system
• fewer than expected number of pups


Mouse Genome Informatics
cx3
    Acadltm1Uab/Acadltm1Uab
Acadvltm1Uab/Acadvltm1Uab

involves: 129S6/SvEvTac * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• partially cannibalized pups are observed, indicating loss occurs as late as the periparturient period