Rescue of the murine amelogenin null phenotype with two amelogenin transgenes

The amelogenin proteins are required for normal enamel development; the most abundant amelogenins expressed from alternatively spliced mRNAs are M180 and leucine rich amelogenin protein (LRAP). The Amelx null (KO) mouse has an enamel defect similar to human X-linked amelogenesis imperfecta. The disorganized enamel layer in KO mice is 10–20% the thickness of wild-type (WT) enamel and lacks prismatic structures. When the KO mice were mated with mice that express TgM180-87, partial rescue of the phenotype was observed such that enamel thickness, volume and density increased. A second transgene was introduced by mating the TgM180KO mice with TgLRAP mice, and male offspring were characterized for genotype and tooth phenotype was evaluated by SEM. TgM180LRAPKO molar enamel thickness further increased, and the structure was improved, with a more defined decussation pattern compared to singly rescued mice. We conclude that TgM180 provides significant rescue of the KO phenotype. Although the effectiveness of TgLRAP to rescue by itself is less obvious, the addition of TgLRAP to TgM180 in KO enamel leads to added improvement in both amount and structure and thus these transgenes function in a complementary manner. Together the two most abundant amelogenins lead to formation of obvious enamel decussation patterns.