The Amelogenin Proteins and Enamel Development in Humans and Mice
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概要
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Before a tooth erupts into the oral cavity, the mineralized enamel and dentin layers begin to develop. During these early stages of enamel formation, an abundant group of proteins known as amelogenins are secreted by ameloblast cells within the developing tooth. These proteins are required for the enamel layer to reach its normal thickness and attain its intricate structure. Human patients with amelogenin gene mutations have a condition referred to as amelogenesis imperfecta, and we have analyzed human gene defects so that we can recreate them in mice. We have generated mice with a null amelogenin mutation where no amelogenin is produced, mice that over-express normal and mutated amelogenins, and over-expressors have been mated to null mice for rescue experiments. Because there are at least 15 messages that are alternatively spliced from a single amelogenin primary RNA transcript, these approaches have begun to reveal the functions of individual amelogenin proteins during enamel development. Finally, amelogenins are processed by carefully regulated proteolytic digestion leading to many additional amelogenin peptides and it is likely that protein function is altered during this developmental process. We have also had some surprises, as one of our mouse models develops odontogenic tumors, and we know now that some of the amelogenins are expressed in other regions of the body outside of the oral cavity, and may have a role in signal transduction.
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