Osteoporosis is a disorder of bone turnover and the most common skeletal disease. Since the function of bone cells is controlled by specific molecules, UKE group's general aim is to identify these in order to establish targets for drugs to increase bone mass. Here it is particularly relevant to identify mutations in genes that cause specific skeletal disorders with altered bone cell activities. In the last decade many of such gene mutations have been reported, and some of these findings have led to the development of new drugs that can be utilized to treat osteoporosis and other skeletal disorders. Within SYBIL UKE will focus our research on two molecules controlling bone mass in humans. One of these is the receptor molecule NOTCH2, whose gene mutation causes Hajdu-Cheney-syndrome, a disease characterized by early-onset osteoporosis. The other molecule is WNT1, a growth factor potentially binding to a receptor known as LRP5. Mutations of the WNT1 and LRP5 gene have been found in a large number of individuals with either osteoporosis or high bone mass, which demonstrates their importance in controlling bone formation. The function of the three molecules will be analyzed in mouse models of the corresponding diseases, and results obtained here will be applied to study and/or to treat individuals with various skeletal disorders.