Researchers Find Enzyme is Key to Dental Enamel Formation in Mice

Dec. 18, 2002
Findings have implications for human enamel disease.

A team of scientists from The Forsyth Institute and the National Institute of Dental and Craniofacial Research (NIDCR) have discovered that an enzyme known as matrix metalloproteinase-20 (MMP-20) is essential for proper formation and development of dental enamel in mice.

Since MMP-20 is expressed in human teeth, the finding, in studies of MMP-20 "knockout" mice, may be relevant to science's understanding of a human disease known as amelogenesis imperfecta (AI), which causes one in approximately 7000 children to be born with defective dental enamel, according to John Bartlett, PhD., Associate Member of the Staff at The Forsyth Institute, and the principal investigator.

In the US, the teeth of such children are ordinarily capped. Left untreated, the disease results in pain and eventual loss of teeth. Because of similarities between the mouse and human genomes, "it is possible that loss of this enzyme in humans would cause this disease, " Bartlett said.

The finding is also significant because the family of MMP enzymes is involved in degrading almost all tissues of the body, Bartlett said, and is important in tissue turnover and replacement. "Understanding how MMP-20 relates to proper enamel formation may help scientists understand the importance of other MMP enzymes to normal development or in disease states such as cancer, where MMPs are known to be involved in tumor metastasis," Bartlett said.

Team members included Zeidonis Skobe, Associate Member of the Staff at The Forsyth Institute; Dr. Henning Birkedal-Hansen, Scientific Director of the National Institute of Dental and Craniofacial Research (NIDCR), and John J. Caterina, postdoctoral researcher, also of the NIDCR. Drs. Birkedal-Hansen and Caterina developed the knockout (MMP-20-deleted) mice that were key to this study.

The article, "Enamelysin (MMP-20) deficient mice display an amelogenesis imperfecta phenotype

will be published in the January/February 2003issue of the Journal of Biological Chemistry, published on December 20, 2002. It is available at

In addition to his full-time appointment at Forsyth, where the current research was carried out, Dr. Bartlett is an assistant professor in the Department of Oral and Developmental Biology at the Harvard School of Dental Medicine.