An amelogenin mutation leads to disruption of the odontogenic apparatus and aberrant expression of Notch1.

Abstract

BACKGROUND:

Amelogenins are highly conserved proteins secreted by ameloblasts in the dental organ of developing teeth. These proteins regulate dental enamel thickness and structure in humans and mice. Mice that express an amelogenin transgene with a P70T mutation (TgP70T) develop abnormal epithelial proliferation in an amelogenin null (KO) background. Some of these cellular masses have the appearance of proliferating stratum intermedium, which is the layer adjacent to the ameloblasts in unerupted teeth. As Notch proteins are thought to constitute the developmental switch that separates ameloblasts from stratum intermedium, these signaling proteins were evaluated in normal and proliferating tissues.

METHODS:

Mandibles were dissected for histology and immunohistochemistry using Notch1 antibodies. Molar teeth were dissected for western blotting and RT-PCR for evaluation of Notch levels through imaging and statistical analyses.

RESULTS:

Notch1 was immunolocalized to ameloblasts of TgP70TKO mice, KO ameloblasts stained, but less strongly, and wild-type teeth had minimal staining. Cells within the proliferating epithelial cell masses were positive for Notch1 and had an appearance reminiscent of calcifying epithelial odontogenic tumor with amyloid-like deposits. Notch1 protein and mRNA were elevated in molar teeth from TgP70TKO mice.

CONCLUSION:

Expression of TgP70T leads to abnormal structures in mandibles and maxillae of mice with the KO genetic background and these mice have elevated levels of Notch 1 in developing molars. As cells within the masses also express transgenic amelogenins, development of the abnormal proliferations suggests communication between amelogenin producing cells and the proliferating cells, dependent on the presence of the mutated amelogenin protein.

• Authors: Xu Chen, Yong Li, Faizan Alawi, Jessica R Bouchard, Ashok B Kulkarni, Carolyn W Gibson
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 40 Issue 3 Pg. 235-42 (Mar 2011) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 20923441 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Amelogenin
• Notch1 protein, mouse
• Receptor, Notch1
• Threonine
• Proline

Topics

• Ameloblasts (pathology)
• Amelogenesis (genetics)
• Amelogenin (genetics)
• Animals
• Blotting, Western
• Cell Proliferation
• Dental Enamel (embryology)
• Enamel Organ (pathology)
• Epithelial Cells (pathology)
• Exons (genetics)
• Female
• Gene Expression Regulation, Developmental (genetics)
• Genotype
• Male
• Mice
• Mice, Knockout
• Mice, Transgenic
• Molar (pathology)
• Point Mutation (genetics)
• Proline (genetics)
• Receptor, Notch1 (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Threonine (genetics)
• Tooth Eruption (genetics)
• Tooth Germ (pathology)
• Tooth, Unerupted (pathology)
• Transgenes (genetics)