Mouse Gene Mapping: Bone, Obesity, and Leptin
Osteoporosis is a disease of low bone mass and strength that leads to increased risk of fracture. Four key risk factors for osteoporotic fractures are sex, age, family history, and obesity. Risk of fracture is higher in women than in men, increases with age and a family history of low bone mass, and decreases with increased obesity. However, relationships among these factors remain unclear. Are obesity and bone properties affected by a common set of genes and/or environmental factors? Is the relationship determined mechanically through the general effects of weight on bone or is there a specific, physiological relationship between fat and bone? What is the role of leptin in the obesity-bone relationship? We are examining the relationship between bone mass, morphology and biomechanics, and gender, genetics, and obesity in a murine model of hereditary and dietary obesity, the LGXSM Recombinant Inbred (RI) strains and an Advanced Intercross (AI) Line reared on high- and low-fat diets. We are examining the effects of both genetic and environmental (dietary) factors on bone mass, morphology, and biomechanics and examining how genes and environments affect the relationship between bone properties and obesity. While obesity is an important factor in osteoporotic fracture risk, it is not clear which pathways modulate the relationship between obesity and bone. Nearly all murine studies of this issue have focused on two specialized mouse mutants, obese (ob/ob) and diabetes (db/db). While these studies have been invaluable, both models involve complete loss of leptin signaling and may not be representative of obesity-bone relationships when leptin levels vary within a more physiologically normal range. By examining the genetic and environmental basis of variation in bone properties in a mouse obesity model, we will uncover new genetic pathways involved in the association of obesity, leptin and bone.
Supported by NIDDK grant DK75112
Dr. Matt Silva, Washington University
Publications on the Topic
Reich, M. S.; J. P. Jarvis, M. J. Silva and J. M. Cheverud. 2008. Genetic relationships between obesity and osteoporosis in LGXSM Recombinant Inbred mice. Genetics Research 90: 433-444.
Carson, E. A., Kenney-Hunt, J. P., Pavlicev, M.; Bouckaert, K. A., Chinn, A. J., Silva, M. J., Cheverud, J. M. 2012. Weak genetic relationship between trabecular bone morphology and obesity in mice. Bone 51: 46-53.