Nature Genetics
19, 271 - 273 (1998)
doi:10.1038/956
Mutation in Npps in a mouse model of ossification of the posterior
longitudinal ligament of the spineAkihiko Okawa1, 2, Isao Nakamura1, 3, Sumio Goto2, Hideshige Moriya2, Yusuke Nakamura1
& Shiro Ikegawa11
Laboratory of Molecular Medicine, Human Genome Center,
Institute of Medical Science, The University of Tokyo, 4-6-1
Shirokanedai, Minato-ku, Tokyo
108, Japan. 2
Department of Orthopaedic Surgery, Chiba University
School of Medicine, Inohana 1-8-1, Chyuo-ku,
Chiba, 260, Japan. 3
Department of Orthopaedic Surgery, Shinshu University
School of Medicine, Asahi 3-1-1, Matsumoto-shi,
Nagano, 390, Japan.
Correspondence should be addressed to Yusuke Nakamura yusuke@ims.u-tokyo.ac.jpOssification of the posterior longitudinal ligament of the spine (OPLL)
is a common form of human myelopathy caused by a compression of the spinal
cord by ectopic ossification of spinal ligaments1,
2. To elucidate
the genetic basis for OPLL, we have been studying the ttw (tiptoe walking;
previously designated twy) mouse, a naturally occurring mutant which
exhibits ossification of the spinal ligaments very similar to human OPLL (Refs 3,4). Using a positional candidate-gene
approach, we determined the ttw phenotype is caused by a nonsense mutation
(glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase.
This enzyme regulates soft-tissue calcification and bone mineralization by
producing inorganic pyrophosphate, a major inhibitor of calcification5,
6,
7,
8. The accelerated bone formation characteristic of ttw
mice is likely to result from dysfunction of NPPS caused by predicted
truncation of the gene product, resulting in the loss of more than one-third
of the native protein. Our results may lead to novel insights into the mechanism
of ectopic ossification and the aetiology of human OPLL.
|
