Phenotypes Associated with This Genotype

Genotype
MGI:3693216

• Allelic Composition: Acadm^tm1Uab/Acadm^tm1Uab
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

Histopathology of wild-type and Acadm^tm1Uab/Acadm^tm1Uab mice.

mortality/aging

postnatal lethality, incomplete penetrance ( J:115759 )

• about 60% of homozygous animals are lost prior to weaning, compared to about 2% of wild-type

homeostasis/metabolism

impaired adaptive thermogenesis ( J:115759 )

• after an 18 hour fast, mutants placed at 4 degrees for 3 hours have an average rectal temperature of 23.4 degrees Celsius vs 35 degrees for wild-type; some fatalities occurred in mice (3/5) with temperatures of 16.7-19.2 degrees Celsius

abnormal blood homeostasis ( J:115759 )

• mutants have significantly elevated levels of organic acids such as adipic, suberic and sebaic acids

increased circulating carnitine level ( J:115759 )

• levels of serum decenoylcarnitine are elevated 5- to 6-fold in mutants

decreased circulating glucose level ( J:115759 )

• serum levels are lower than in wild-type; however, this is not statistically significant

cardiovascular system

abnormal aorta elastic tissue morphology ( J:115759 )

• multifocal degeneration of elastic tissue in aorta at base of heart is observed in severely affected mice

• this is accompanied by multifocal collections of globular translucent yellow-brown pigment (ceroid lipofuscin); similar deposits are scattered within adjacent adipose tissue

abnormal myocardial fiber morphology ( J:115759 )

• degenerating myocytes may display swelling and replacement of myocardial fibrils with finely granular eosinophilic material

• nuclei of affected myocytes are large, pale, and vesicular with prominent nucleoli

myocardial fiber degeneration ( J:115759 )

• some mutants show cardiomyopathy with chronic multifocal myocyte degeneration and necrosis

cardiac fibrosis ( J:115759 )

• in severely affected regions, fibrosis accompanies myocyte loss

cardiomyopathy ( J:115759 )

• multiple mutants display diffuse cardiomyopathy

liver/biliary system

macrovesicular hepatic steatosis ( J:115759 )

• after a 24 hour fast, 6-8 week-old mutants exhibit diffuse macrovesicular hepatic steatosis

microvesicular hepatic steatosis ( J:115759 )

• after a 24 hour fast, 6-8 week-old mutants exhibit diffuse microvesicular hepatic steatosis

muscle

abnormal myocardial fiber morphology ( J:115759 )

• degenerating myocytes may display swelling and replacement of myocardial fibrils with finely granular eosinophilic material

• nuclei of affected myocytes are large, pale, and vesicular with prominent nucleoli

myocardial fiber degeneration ( J:115759 )

• some mutants show cardiomyopathy with chronic multifocal myocyte degeneration and necrosis

cardiomyopathy ( J:115759 )

• multiple mutants display diffuse cardiomyopathy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medium chain acyl-CoA dehydrogenase deficiency		DOID:0080153	OMIM:201450	J:115759