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Urokinase-type Plasminogen Activator mRNA is Expressed in Normal Developing Teeth and Leads to Abnormal Incisor Enamel in αMUPA Transgenic Mice

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Abstract

The urokinase-type plasminogen activator (uPA) is a secreted, inducible serine protease implicated in extracellular proteolysis and tissue remodeling. Here we detected uPA mRNA through in situ hybridization in developing molar and incisor teeth of normal mice at multiple sites of the cap and bell developmental stages. The mRNA was confined to epithelial cells, however, was undetectable in ameloblasts or their progenitor preameloblasts and the inner enamel epithelium. Furthermore, mice of five lines of previously described αMUPA transgenic mice, carrying a transgene consisting of the uPA cDNA linked downstream from the αA-crystallin promoter, overexpressed uPA mRNA in the same epithelial sites. In addition, αMUPA mice showed remarkably high levels of uPA mRNA in ameloblasts, however, exclusively in two specific sites late in incisor development. First, at the late secretory stage, but only on sides of the ameloblast layer. Second, in a limited zone of ameloblasts near the incisal end, coinciding with a striking morphological change of the ameloblast layer and the enamel matrix. In adult αMUPA mice, the incisor teeth displayed discoloration and tip fragility, and reduction of the outer enamel as determined by scanning electron microscopy. These results suggest that balanced uPA activity could play a role in normal tooth development. The αMUPA tooth phenotype demonstrates a remarkable sensitivity to excessive extracellular proteolysis at the incisor maturation stage of amelogenesis.

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Authors and Affiliations

  1. Department of Biological Chemistry, Weizmann Institute of Science, 76100, Rehovot, Israel

    Ruth Miskin, Tamar Masos & Zipi Shoham

  2. Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD, 20892, USA

    Lisa Williams-Simons

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  1. Ruth Miskin
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  2. Tamar Masos
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  3. Zipi Shoham
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  4. Lisa Williams-Simons
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Correspondence to Ruth Miskin.

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Miskin, R., Masos, T., Shoham, Z. et al. Urokinase-type Plasminogen Activator mRNA is Expressed in Normal Developing Teeth and Leads to Abnormal Incisor Enamel in αMUPA Transgenic Mice. Transgenic Res 15, 241–254 (2006). https://doi.org/10.1007/s11248-006-0006-3

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