During enamel development, an extracellular matrix is secreted by the ameloblasts. The amelogenin proteins are the principle organic constituent of this matrix, and these proteins are thought to be involved in regulation of size and growth of enamel crystals. The amino acid sequence of the amelogenin proteins is conserved in divergent species, perhaps to preserve the protein structure in order to provide a specific function during enamel formation or maturation. since most of the amelogenin protein is not present in mature enamel, it is likely that proteolytic degradation occurs as mineral forms. The amelogenin proteins that are extracted from developing teeth therefore represent a mixture of newly synthesized and partially degraded proteins. In this proposal we describe experiments designed to study amelogenin expression at the level of mRNA. The bovine X-chromosomal primary transcript is alternatively spliced, and we propose to evaluate levels of the 4 mRNAs so far identified. We will also study levels of the bovine Y-chromosomal mRNA, and search for additional alternative splice products. Isolation of the bovine Y-chromosomal amelogenin gene will allow us to verify the sequence of the Y-linked cDNA obtained by PCR, and to compare gene structure to that of the X-chromosomal gene. In addition, we plan to evaluate certain human odontogenic tumors for expression of amelogenin mRNA, in order to clone human cDNAs to determine whether the human Y-linked gene is active and whether alternative splicing occurs also in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE010149-02
Application #
3223774
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1992-04-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Gibson, C W; Collier, P M; Yuan, Z A et al. (1998) DNA sequences of amelogenin genes provide clues to regulation of expression. Eur J Oral Sci 106 Suppl 1:292-8
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Gibson, C W; Collier, P M; Yuan, Z A et al. (1997) Regulation of amelogenin gene expression. Ciba Found Symp 205:187-97; discussion 197-9
Collier, P M; Sauk, J J; Rosenbloom, S J et al. (1997) An amelogenin gene defect associated with human X-linked amelogenesis imperfecta. Arch Oral Biol 42:235-42
Yuan, Z A; Collier, P M; Rosenbloom, J et al. (1996) Analysis of amelogenin mRNA during bovine tooth development. Arch Oral Biol 41:205-13

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