Scientists home in on tooth enamel gene
Applying a new molecular "probe" to human chromosomes, researchers have found the approximate location of the gene that tells cells to make the major protein in tooth enamel. The protein, called amelogenin, is one of two proteins that provide the biological scaffolding around which mineralization occurs during tooth development. Many scientists believe it plays an active, regulatory role in tooth development as well.
The researchers say a determination of the gene's exact location should boost their understanding of a rare, hereditary weakness of tooth enamel called amelogenesis imperfecta. And because tooth enamel mineralization resembles the process of bone formation, isolation of the amelogenin gene may aid in detecting genes involved in inherited bone defects.
Enamel, the outermost coating of teeth, forms the hardest tissue in the vertebrate body. Its production begins with a matrix of amelogenin, produced by cells called ameloblasts, along with the less abudant protein enamelin. During the process of enamel maturation, the proteins are gradually replaced by crystals of a mineral compound called hydroxyapatite.
Mature teeth are composed of about 99 percent mineral crystals and less than 1 percent protein. But while present, amelogenin plays key roles in tooth development, perhaps in part by helping to exclude water from tooth tissue. Water content affects the size and arrangement of hydroxyapatite crystals.
Eduardo C. Lau of the University of Southern California in Los Angeles and his colleagues used a genetic probe made from mouse amelogenin DNA to look for a similar sequence on human chromosomes. The experiments allowed Lau and his co-workers to narrow the human amelogenin gene's location to relatively small genetic "neighborhoods" on both the X and Y chromosomes in humans -- neighborhoods where other genes affecting tooth morphology are known to reside.
Once the researchers find the gene's exact location, they hope to pursue one or more molecular biological approaches to understanding the exact role amelogenin plays in biomineralization and the types of gene defects that can disrupt tooth development. Experiments could involve genetically engineered mice that either under-or overproduce the human protein, or that produce various defective versions of the protein, Lau told SCIENCE NEWS.
Meanwhile, the researchers continue to study people with amelogenesis imperfecta in families known to carry the tooth defect. The disorder, which leaves teeth with little or no enamel coating, affects about one in 14,000 individuals in the United States.
A precise identification of the amelogenin gene could lead to a genetic test capable of screening for the disease in members of high-risk families, says Lau, who reports the new findings in GENOMICS (Vol. 4, No. 2).
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