Role of the mouse ank gene in control of tissue calcification and arthritis

Mutation at the mouse progressive ankylosis (ank) locus causes a generalize d, progressive form of arthritis accompanied by mineral deposition, formati on of bony outgrowths, and joint destruction. Here, we show that the ank Lo cus encodes a multipass transmembrane protein (ANK) that is expressed in jo ints and other tissues and controls pyrophosphate levels in cultured cells. A highly conserved gene is present in humans and other vertebrates. These results identify ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals.