Functional domains for amelogenin revealed by compound genetic defects.
We have previously used the yeast two-hybrid assay and multiple in vitro methodologies to show that amelogenin undergoes self-assembly involving two domains (A and B). Using transgenic animals, we show that unique enamel phenotypes result from disruptions to either the A- or B-domain, supporting the role of amelogenin in influencing enamel structural organization. By crossbreeding, animals bearing two defective amelogenin gene products have a more extreme enamel phenotype than the sum of the defects evident in the individual parental lines. At the nanoscale level, the forming matrix shows alteration in the size of the amelogenin nanospheres. At the mesoscale level of enamel structural hierarchy, 6-week-old enamel exhibits defects in enamel rod organization caused by perturbed organization of the precursor organic matrix. These studies reflect the critical dependency of amelogenin self-assembly to form a highly organized enamel organic matrix, and that amelogenins engineered to be defective in self-assembly produce compound defects in the structural organization of enamel.
Paine
Michael L
ML
Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California 90033-1004, USA. paine@hsc.usc.edu
Luo
Wen
W
Zhu
Dan-Hong
DH
Bringas
Pablo
P
Snead
Malcolm L
ML
D053523:Amelogenin; D000818:Animals; D003743:Dental Enamel / Q000648:ultrastructure; D003746:Dental Enamel Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D051379:Mice; D008854:Microscopy, Electron; D036103:Nanotechnology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes
D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins