FUNCTION OF THE LIM-HOMEODOMAIN GENE LMX1B IN HUMAN GENETIC DISEASE AND KIDNEY DEVELOPMENT

Nail Patella syndrome (NPS) is an inheritable human genetic disease. It affects mainly the skeletal system, including joints and knee caps, nails and kidneys. Recently, the gene responsible for this disease has been identified and named LMX1B. It is very important for the correct development of the limbs, but it is also expressed in the brain and kidney. Scientists have generated a mouse model showing the same characteristics of the human disease. These animals are useful for gaining a better understanding of the function of the gene responsible for NPS. In particular, the presence of the same defect in the mouse and human kidneys helped to discover a novel and important function for this gene during kidney development. Ultimately, the kidney disease represents the major complication of the NPS and may require an organ transplantation. The main goal of this project is to discover genes that are affected by the alteration of Lmx1b expression in the kidney and genes that are able to modulate the function of Lmx1b in this organ. These studies will be performed using comparative analyses between the aforementioned mouse model and normal mice, as a control. The results of the proposed project will improve our understanding in renal physiology and ultimately help in finding new therapies for kidney diseases in general. They will also be useful for genetic counseling of families affected by NPS.