International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 177 - BONE DEFECTS IN DYSMORPHOLOGY MUTANT MICE FROM THE MUNICH ENU-MUTAGENESIS SCREEN

Abe K, Grundner-Culemann E, Gailus-Durner V, Fuchs H, Hrabé de Angelis M

Institute of Experimental Genetics, GSF National Research Center, Neuherberg, Germany

Bone remodelling is a dynamic process in which new bone is added and old bone is removed.  In humans, the bone formation dominates the bone resorption until the age of twenties when the bone mass reaches a maximum.  The bone mass remains stable for years, and starts to decrease after a certain age. Balance between formation and resorption is regulated by multiple complex systems which include growth factors, hormones, and vitamins. Although defects in bone remodeling in humans such as osteoporosis cause deterioration of quality of life in old age, its mechanisms remain incompletely understood. In a large scale mouse ENU-mutagenesis project, we use 49 visible morphological parameters for mutant screening. So far, 260 dysmorphological mutant lines have been isolated and confirmed. To identify mouse models for human bone diseases, we have started a secondary screening of existing mutant lines in the dysmorphology module of the German Mouse Clinic. Additional bone-related parameters include x-ray radiography, dual-energy x-ray absorptiometry (DEXA), micro-computer tomography, and physiological analysis. We selected mutant lines showing bone-related phenotypes for this screening. One mutant line, Ali14 (abnormal limb) mutant mice showed decreased bone mass density (p<0.001), weight (p<0.001), fat and lean mass (p<0.001), and body size (p<0.001) were detected. Ali14 is a dominant mutation, and only mutant males exhibit swelling on  hind feet and spotted ears around 4 months of age. Homozygous animals have not been detected. By histological examination, inflammatory infiltrations were detected in joints, skin, and bone marrow of hind feet in Ali14 mice. These results suggest that Ali14 mutant mice could be a mouse model for generalized bone loss in inflammatory arthritis. Further detailed analysis using micro-computed tomography for Ali14 mice is underway. We will present a recent update of bone-related screening, and the possible involvement of detected phenotypes in human bone disease will be discussed.

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