KALLMANN SYNDROME GENES IN CAENORHABDITIS ELEGANS AND DROSOPHILA MELANOGASTER

Kallmann Syndrome (KS) is a genetic disease characterized by anosmia and hypogonadism. Three familial forms are known. The human gene responsible for the X-linked form of the disease has been identified. Very little is known about the mechanism of action of its product, the protein KAL, at the molecular and cellular level. We have focused on the Kal homolog genes in the nematode Caenorhabditis elegans and in the insect Drosophila melanogaster. The structure of the genes, the cells that express them and the phenotypes of mutants have been determined. We have shown that the human gene can compensate for the loss of the nematode one. Our studies provide two animal models in which the function of Kal genes can be studied, both amenable to genetic and molecular analysis of development. The aims of the program are: to understand the function of Kal; to identify other molecules with which it interacts, and to elucidate some aspects of the biochemical properties of KAL proteins. The long term objectives of the project are: a) an understanding of KAL function at the molecular and cellular level detailed enough to be useful to explain the pathogenesis of all the symptoms of the disease; b) the identification of the genes responsible for the other genetic forms of Kallmann Syndrome, which are more frequent than the X-linked form. These long term objectives would be relevant from a health care point of view as they can provide diagnostic tools for the non-X-linked form of KS and suggest new ideas and strategies for the management of all the clinical symptoms of KS patients as well as of patients with other neurological disorders.