Heriditary dental disorders

Scientists from NIDCR have created an animal model that mimics two human hereditary dental defects-dentinogenesis imperfecta type II and dentin dysplasia. Dr. Ashok Kulkarni and his colleagues genetically engineered mice that make extra amounts of TGF-b1 (transforming growth factor beta-1) in their teeth. The animals were born with no apparent defects, but at two weeks their teeth became discolored and eventually fractured, leaving behind small stumps. Specialized study of the animals showed reduced activity of the dspp gene, which produces a protein that is dire for dentin formation.

Dentinogenesis imperfecta type II, which affects approximately 1 in 6,000 newborns, is characterized by blue-gray or amber brown opaque teeth. The teeth have narrow roots, are frail and fracture easily. In dentin dysplasia, tooth color can be normal, or slightly bluish or brownish and opaque. The teeth are shorter and more pointed than normal teeth, and may become loose and fall out because of inadequate root formation. The tooth's dentin is abnormal in both hereditary defects.

Tests revealed that dspp activity was substantiallyy reduced in the mouse model compared to normal animals. "This is the first time that overproduction of TGF-b1 in teeth has been shown to result in reduced functioning of the dspp gene," Dr. Kulkarni said. "We think the gene might contain elements that respond to TGF-b1. Or perhaps other genes, influenced by TGF-b1, may indirectly control dspp." TGF-b1 is a member of the superfamily of TGF proteins that have many diverse functions in normal development throughout the body. It has long been known that TGF-b1 plays a part in tooth development and that it is active in the dentin-forming cells from as early as day 13 in the mouse embryo.

The research team will continue to study the regulation of the dspp gene found in the development of dentinogenesis imperfecta type II and dentin dysplasia, as well as other genetic and molecular aspects of the disorders.