Obesity, non-insulin dependent diabetes mellitus (NIDDM) and heart disease are highly prevalent metabolic diseases that afflict a large proportion of the aging population in the United States. These diseases should be viewed as aspects of a metabolic syndrome that is produced by the interaction of many genes, rather than as separate entities. To illustrate the complexity of the issue, there are approximately 500 to 1,000 genes in mice that may lead to obesity when mutated. Our program focuses on identification of new obesity and type 2 diabetes mutations and their genetic modifiers. We are investigating aspects of sensory loss in addition to the biochemical obesity and type 2 diabetes pathways in Alström and similar genetic syndromes. Our laboratory identified a human gene, ALMS1, that is mutated in patients with Alström syndrome, a rare inherited condition characterized by multiple disorders, including childhood obesity, retinal and cochlear (inner ear) degeneration, type 2 diabetes and hyperlipidemia (elevation of fats in the bloodstream, including cholesterol and triglycerides).
Mouse models of vision research have been instrumental in identifying primary mutations within genes that lead to ocular disorders and in identifying pathways important in retinal function through modifier screens, protein, and expression profiling. Our program is dedicated to identifying genes which when mutated lead to ocular diseases, to identify mechanisms underlying the function of those genes as well as the resulting pathological changes. The models are derived both from spontaneous mutations as well as chemical mutagenesis screens. Our lab focuses primarily on genes affecting the neural retina and supporting structures such as the retinal pigmented epithelium, glial cells and vascular network.