AbstractPreviously, it was shown that the volume of forming enamel of molar teeth in biglycan‐null mice was greater than that in genetically matched wild‐type mice. This phenotypic change appeared to result from an increase in amelogenin expression, implying that biglycan directly influences amelogenin synthesis. To determine whether biglycan overexpression resulted in decreased amelogenin expression, we engineered transgenic mice to overexpress biglycan in the enamel organ epithelium. Biglycan overexpression did not significantly affect the amelogenin expression in incisor and molar teeth in 3‐day postnatal transgenic mice. In the transgenic animals, we observed that the immature and mature enamel appeared normal. These results suggested that increasing the biglycan expression, in the cells that synthesize the precursor protein matrix for enamel, has a negligible influence on amelogenesis. Anat Rec, 2008. © 2008 Wiley‐Liss, Inc.