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.