Mouse Genome Informatics
hm1
    Acadmtm1Uab/Acadmtm1Uab
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Histopathology of wild-type and Acadmtm1Uab/Acadmtm1Uab mice.

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

homeostasis/metabolism
• in severely affected regions, fibrosis accompanies myocyte loss
• 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
• mutants have significantly elevated levels of organic acids such as adipic, suberic and sebaic acids
• levels of serum decenoylcarnitine are elevated 5- to 6-fold in mutants
• serum levels are lower than in wild-type; however, this is not statistically significant

cardiovascular system
• 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
• 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
• some mutants show cardiomyopathy with chronic multifocal myocyte degeneration and necrosis
• in severely affected regions, fibrosis accompanies myocyte loss
• multiple mutants display diffuse cardiomyopathy

liver/biliary system
• after a 24 hour fast, 6-8 week-old mutants exhibit diffuse microvesicular and macrovesicular hepatic steatosis

muscle
• 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
• some mutants show cardiomyopathy with chronic multifocal myocyte degeneration and necrosis
• multiple mutants display diffuse cardiomyopathy