Tooth Enamel Defects in Mice with a Deletion at the Arhgap6/AmelX Locus

The amelogenin proteins regulate enamel mineral formation in the developing tooth. The human AMELX gene, which encodes the amelogenin proteins, is located within an intron of the Arhgap6gene. ARHGAP6 encodes a RhoGAP, which regulates activity of RhoA, a small G protein involved in intracellular signal transduction. Mice were generated in which the entire ARHGAP6 gene was deleted by Cre-mediated recombination, which also removed the nested AmelX gene. Enamel from these mice appeared chalky white, and the molars showed excessive wear. The enamel layer was hypoplastic and nonprismatic, whereas other dental tissues had normal morphology. This phenotype is similar to that reported for AmelX null mice, which have a short deletion that removed the region surrounding the translation initiation site, and resembles some forms of X-linked amelogenesis imperfecta in humans. Analysis of the enamel from the Arhgap6/AmelX-deleted mice verifies that the AmelX gene is nested within the murine Arhgap6 gene and shows that removal of the entire AmelX gene leads to a phenotype similar to the earlier AmelX null mouse results, in which no amelogenin protein was detected. However, an unusual layer of aprismatic enamel covers the enamel surface, which may be related to the 1.1-Mb deletion, which included Arhgap6 in these mice.