International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 7 - THE HIGH BODY WEIGHT SELECTED MOUSE LINE DU6 IS A POLYGENIC MODEL FOR GROWTH AND OBESITY

Dr Gudrun A. Brockmann
Research Institute for the Biology of Farm Animals
Wilhelm-Stahl-Allee 2
Dummerstorf 18196 Germany

Co-Authors:  Bevova M and Renne U
Institution:   Research Institute for the Biology of Farm Animals

The main aim of our research is the identification of genetic and physiological factors responsible for increased body weight and obesity at the juvenile age. As model animals we study the high body weight selected mouse line DU6 which contains the biggest mice known world-wide. DU6 is characterized by high body mass and obesity with hyperinsulinemia, hyperleptinemia, and elevated serum concentrations of IGF-I, IGF binding proteins (BPs), and cholesterol. Linkage analysis in intercrosses between the extreme high growth mouse line DU6 and its inbred derivate DU6i, and the unselected control lines DUKs and DBA/2 revealed evidence for many loci influencing body composition as well as serum concentrations of leptin, insulin, IGF-I, IGFBPs, and cholesterol. The individual phenotype reflects the direct effects of QTLs and the effect of a complex net of gene actions. The individual loci that contribute to such variation have small effects only. We have identified significant interaction effects between different QTLs by statistical tests. At present, we are dissecting the complex phenotype by constructing a set of chromosome substitution strains (CSS) for line DU6i. After five generations of recurrent backcrossing to DBA/2, sub-phenotypes are seen which show chromosome-wise effects on body weight. The CSS are a starting point for subsequent isolation of single QTLs and the analysis of epistasis between QTLs by crossing of specific strains.


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