Metabolic phenotyping of an overweight mouse line originated from ethyl-nitroso-urea (ENU) mutagenesis

The Metabolic Laboratory of the German Mouse Clinic performs a comprehensive analysis of energy balance in mouse mutants. It is based on the conflation of different calorimetrical systems for investigation of disturbances in body weight regulation, metabolism and body composition. We investigated an overweight mouse mutant line which originated from the Munich ENU Mutagenesis project. At the age of 18 weeks body weight (BW) of control males (n=8) was 35.4±0.1g (means±sem) and of females (n=7) 26.6±0.9g. The mean BW of mutant males (n=6) was 45.6±0.3g and of females (n=6) 35.6±0.5g. The daily metabolized energy per mouse did not differ between mutants (males: 66.9±3.4 kJ*d-1, females: 68.7±5.4 kJ*d-1) and controls (males: 66.9±3.4 kJ*d-1, females: 62.4±1.9 kJ*d-1). At an ambient temperature of 24°C the resting metabolic rate of mutant mice was lower than expected for the respective BW (control males: 1.68±0.13 kJ*h-1, females: 1.66±0.10 kJ*h-1. Mutant males: 1.67±0.07 kJ*h-1, females : 1.47±0.01 kJ*h-1). In mutant mice a higher blood glucose level indicated diabetes. To reveal a possible resistance to insulin an oral glucose tolerance test will be accomplished. Mutant mice also showed a significantly elevated serum alanine aminotransferase activity which could be an indication of a fatty liver. The serum levels of total cholesterol as well as HDL were significantly increased whereas LDL was only slightly increased.

All measured parameters underline that the overweight phenotype of the mutant mice is associated with a disorder in lipid metabolism.

NGFN2, grant No. 01GR0437 and 01GS0483