Spinal hyperostotic lesions in twy mouse resemble to those observed in human ossification of posterior longitudinal ligament of the spine (OPLL). To investigate pathogenic mechanisms of OPLL, studies have been performed on the spinal lesions of twy mouse. Molecular analyses have shown that osteopontin gene is over-expressed in the spine of twy mouse, and endochondral ossification may not a major process of the spinal lesions. Genetic analyses have shown that twy genotype is caused by a mutation in Npps gene which encodes nucleotide pyrophosphatase. Common polymorphisms in human Npps locus have been analyzed in OPLL patients.