The long term objectives are to determine the molecular mechanisms of dental enamel formation and to identify the genes responsible for amelogenesis imperfecta (AI).
Four specific aims are proposed: 1) to clone and characterize cDNAs encoding porcine enamelin, the 29 kDa calcium binding protein, amelogenin, tuftelin and sheathlin; 2) to clone and characterize the porcine amelogenin gene(s), determine the number of porcine amelogenin gene(s), and their chromosomal localization(s); 3) to clone and characterize human cDNA and genomic clones encoding enamelin and the 29 kDa calcium binding protein (CBP) and to determine their chromosomal localizations; 4) to test for linkage between genes encoding enamel matrix proteins and amelogenesis imperfecta. The amino-terminal sequence of porcine enamel matrix proteins has been provided by a collaborator, Dr. Makato Fukae. The mRNA encoding these proteins are cloned and fully characterized by cloning PCR amplification products, 5' and 3' rapid amplification of cDNA ends (RACE), and by direct screening of a porcine enamel organ epithelia-specific Lambda cDNA library. The porcine amelogenin gene(s) is isolated from a male porcine genomic library. The structure of the gene is determined by the characterization of PCR amplification products, restriction analyses, and DNA sequencing. The number of amelogenin genes is determined by Southern blot analysis. The chromosomal localization is determined by fluorescent in situ hybridization. The human cDNA and genomic clones are isolated from a human tooth-specific cDNA library and a Lambda genomic library. The chromosomal localizations are determined by fluorescent in situ hybridization. Linkage analysis is performed on pedigrees displaying dominantly inherited AI using a candidate gene approach. Specific mutations are identified by single stranded conformatinal polymorphism analysis and characterized by DNA sequencing.
| Chan, Hsun-Liang; Giannobile, William V; Eber, Robert M et al. (2014) Characterization of periodontal structures of enamelin-null mice. J Periodontol 85:195-203 |
| Hu, Jan C-C; Hu, Yuanyuan; Lu, Yuhe et al. (2014) Enamelin is critical for ameloblast integrity and enamel ultrastructure formation. PLoS One 9:e89303 |
| Chan, Albert H-L; Lertlam, Rangsiyakorn; Simmer, James P et al. (2013) Bodyweight assessment of enamelin null mice. Biomed Res Int 2013:246861 |
| Simmer, S G; Estrella, N M R P; Milkovich, R N et al. (2013) Autosomal dominant amelogenesis imperfecta associated with ENAM frameshift mutation p.Asn36Ilefs56. Clin Genet 83:195-7 |
| Simmer, James P; Richardson, Amelia S; Hu, Yuan-Yuan et al. (2012) A post-classical theory of enamel biomineralizationýýý and why we need one. Int J Oral Sci 4:129-34 |
| Hu, Jan C-C; Lertlam, Rangsiyakorn; Richardson, Amelia S et al. (2011) Cell proliferation and apoptosis in enamelin null mice. Eur J Oral Sci 119 Suppl 1:329-37 |
| Smith, Charles E; Hu, Yuanyuan; Richardson, Amelia S et al. (2011) Relationships between protein and mineral during enamel development in normal and genetically altered mice. Eur J Oral Sci 119 Suppl 1:125-35 |
| Chan, H-C; Mai, L; Oikonomopoulou, A et al. (2010) Altered enamelin phosphorylation site causes amelogenesis imperfecta. J Dent Res 89:695-9 |
| Simmer, J P; Papagerakis, P; Smith, C E et al. (2010) Regulation of dental enamel shape and hardness. J Dent Res 89:1024-38 |
| Papagerakis, Petros; Hu, Yuanyuan; Ye, Ling et al. (2009) Identifying promoter elements necessary for enamelin tissue-specific expression. Cells Tissues Organs 189:98-104 |
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