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Tojan Bassam Rahhal

North Carolina State University

Sumoylation of Sp3 is Required for Tooth Development

Sp proteins are responsible for the regulation of a wide variety of genes, many of which play important roles in animal development. One Sp protein, Sp3, has been linked to tooth development. Sp3 encodes three isoforms (Sp3, M1, and M2) that are synthesized from a single mRNA. Each isoform carries the Sp3 DNA-binding domain as well as lysine 551 (K551), the major site of a post-translational modification termed sumoylation. Sumoylation of Sp3 isoforms at K551 has been shown to control Sp3 function in vitro. To determine if sumoylation of Sp3 is required for tooth development, transgenic animals expressing wild-type and mutated Sp3 proteins in ameloblasts, cells important for tooth development and enamel deposition, were created. The focus of my work has been to note the phenotypes of these transgenic strains and correlate resulting phenotypes with the inheritance of each transgene. Interestingly, the teeth of mice carrying a sumoylation-deficient M1 transgene wear rapidly, break easily, and these animals develop a distortion of the alignment of their jaws (malocclusion). Microscopic analyses indicate that the teeth of these animals are coated with an abnormally thin layer of enamel, accounting for their rapid wear and high incidence of breakage. Thus, our results indicate that Sp3 sumoylation is required for proper enamel deposition. Interestingly, the phenotypes of these sumoylation-deficient animals are reminiscent of a human disorder termed amelogenesis imperfecta (AI). Consequently, we believe that our sumoylation-deficient transgenic animals may be a useful model of this debilitating human syndrome.

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