David M. Kingsley, Ph.D.
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Skeletal Disease

     Arthritis, one of the most prevalent diseases in humans, is clearly influenced by genetic factors. Our positional cloning studies of the progressive ankylosis (ank) gene in mice has identified a novel genetic pathway that normally protects joints and articular cartilage from mineralization and joint disease (Ho et al. 2000) . The ank gene encodes a novel, multiple-pass transmembrane protein that stimulates the transport of a small-molecule inhibitor of mineral deposition. The same inhibitor is also used in tartar-control toothpaste to prevent deposition of mineral and calcium deposits along the gum line. Defects in ank remove this "tartar-control" principal from the joints, leading to ectopic mineral deposition in and around joints, and development of arthritis.

     We have found mutations in the human ANK gene that also cause ectopic crystal formation and joint disease (Pendleton et al. 2002). Other groups have found unusual ANK mutations that cause excess bone formation in the skull, with little effect on joints (craniometaphysial dsyplasia). We are investigating how different types of mutations in the ANK gene lead to different molecular, cellular, and clinical phenotypes, and how manipulation of ANK expression and activity may modify susceptibility to arthritis and joint disease (Nociti et al. 2002; Gurley et al. 2006) .

More information on research projects in mice, sticklebacks, and humans.

Stanford University School of Medicine,  Department of Developmental Biology,  279 Capus Drive,  Beckman Center B300,  Stanford, CA,  94305-5329