Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dale LairdAmeloblast differentiation, amelogenesis, connexin, Cx43, enamel organ development, oculodentodigital dysplasia, mouse model of human disease

Abstract

Coordinated differentiation of the enamel organ is essential to enamel deposition and mineralization. This process is likely governed by Cx43-based gap junctional intercellular communication as oculodentodigital dysplasia (ODDD) patients harboring Cx43 mutants exhibit enamel defects. To assess the role of Cx43 in tooth development we employ an ODDD mouse model, Gjal /+, which harbors a G60S Cx43 mutant and exhibits tooth abnormalities mimicking the human disease. Total Cx43 gap junction plaques were reduced in Gjal /+ mouse incisors compared to wild-type littermate controls. Disorganized GjalJrt/+ mouse ameloblasts and abnormal distribution of amelogenin were observed. A thin enamel layer became more apparent after tooth eruption suggesting enamel integrity is compromised. Mutant mouse incisors were longer with a thicker dentin layer, reflecting a mechanical stress response to the depleted enamel layer. Together, these data suggest that Cx43 gap junctions play a role in enamel organ function

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