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The Small Bovine Amelogenin LRAP Fails to Rescue the Amelogenin Null Phenotype

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Abstract

Amelogenins are the most abundant secreted proteins in developing dental enamel. These evolutionarily-conserved proteins have important roles in enamel mineral formation, as mutations within the amelogenin gene coding region lead to defects in enamel thickness or mineral structure. Because of extensive alternative splicing of the primary RNA transcript and proteolytic processing of the secreted proteins, it has been difficult to assign functions to individual amelogenins. To address the function of one of the amelogenins, we have created a transgenic mouse that expresses bovine leucine-rich amelogenin peptide (LRAP) in the enamel-secreting ameloblast cells of the dental organ. Our strategy was to breed this transgenic mouse with the recently generated amelogenin knockout mouse, which makes none of the amelogenin proteins and has a severe hypoplastic and disorganized enamel phenotype. It was found that LRAP does not rescue the enamel defect in amelogenin null mice, and enamel remains hypoplastic and disorganized in the presence of this small amelogenin. In addition, LRAP overexpression in the transgenic mouse (wildtype background) leads to pitting in the enamel surface, which may result from excess protein production or altered protein processing due to minor differences between the amino acid compositions of murine and bovine LRAP. Since introduction of bovine LRAP into the amelogenin null mouse does not restore normal enamel structure, it is concluded that other amelogenin proteins are essential for normal appearance and function.

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Acknowledgements

We thank J. Bartlett and J. Simmer for suggestions and critical comments on the manuscript, T. Tucker for assistance with DNA sequence determination, and J. Richa at the Univ. of Pennsylvania Transgenic Core Facility for production of the transgenic mice. We acknowledge the excellent care by Levy vivarium staff. Support for this work was provided by NIH grants DE11089 (CWG) and DE12879 (JTW).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, 240 S. 40th St., Philadelphia, PA, USA

    E. Chen, Z. -A. Yuan, Y. Li, P. M. Collier, M. D’Angelo, S. Decker, R. Piddington, W. R. Abrams & C. W. Gibson

  2. Department of Pediatric Dentistry, University of North Carolina, Chapel Hill, NC, USA

    J. T. Wright & S. P. Hong

  3. Functional Genomics Unit and Gene Targeting Facility, NIDCR, National Institutes of Health, Bethesda, MD, USA

    B. Hall & A. B. Kulkarni

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  1. E. Chen
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  2. Z. -A. Yuan
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  3. J. T. Wright
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  5. Y. Li
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  12. A. B. Kulkarni
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  13. C. W. Gibson
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Correspondence to C. W. Gibson.

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Chen, E., Yuan, ZA., Wright, J. et al. The Small Bovine Amelogenin LRAP Fails to Rescue the Amelogenin Null Phenotype . Calcif Tissue Int 73, 487–495 (2003). https://doi.org/10.1007/s00223-002-0036-7

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