Laminin‐332 deficient mice present defects during tooth enamel development (LB547)

Abstract

The epithelial ameloblasts are separated from the maturing enamel surface by an atypical basal lamina (BL) that is enriched in laminin (Lm)‐332. This heterotrimeric protein (α3, ß3 and γ2 chains) provides structural integrity to BLs and exerts effects on various epithelial cell processes including cell adhesion. Mouse models that lack expression of individual Lm‐332 chains die shortly after birth. However, recently a viable mouse model of Lm‐332 deficiency has been developed which expresses a doxycycline‐controllable human Lm γ2 transgene under the cytokeratin 14 promoter on the Lm γ2 knockout background (PLoS One 7(9):e45546). To investigate the role of Lm‐332 in enamel development, we examined the upper and lower maxillae from ~8‐week‐old wt and Lm‐332 deficient mice. At the light microscope level, incisors from Lm‐332 deficient mice showed severe structural changes at the level of the enamel organ. In decalcified samples, the organic matrix of forming enamel was altered and residual matrix was found throughout the maturation stage, suggesting Lm‐332 is required for both formation and mineralization of enamel. CT‐scans and scanning electron microscope analyses showed that Lm‐332 deficient mice exhibited hypomineralized enamel layer and occlusal surface wear in molars. The alterations in enamel formation observed in this mouse model are similar to those in teeth of patient with junctional epidermolysis bullosa due to Lm‐332 mutations. These mice will be an invaluable tool to study the role of Lm‐332 in enamel formation and better understand the role of the atypical BL found at cell‐enamel interfaces.Grant Funding Source: Supported by CIHR, NIH/NHLBI P01HL029594, Shriners of North America