Immunocharacterization of the atypical basal lamina at cell‐tooth interfaces in laminin‐332 deficient mice (LB548)

Abstract

Unlike elsewhere in the body, the atypical basal lamina (BL) at epithelial‐tooth interfaces must bind to mineral rather than connective tissue. Therefore, this BL has adapted by integrating specialized components. It is enriched in laminin‐332 (Lm‐332), and recently amelotin (AMTN), odontogenic ameloblast‐associated (ODAM), and secretory calcium‐binding phosphoprotein‐proline‐glutamine‐rich 1 (SCPPPQ1), members of the SCPP gene family, have been identified as novel constituents. To explore how these three small molecular weight proteins participate in BL structure and mediate cell‐mineral adhesion, we used a mouse model of Lm‐332 deficiency, which expresses a doxycycline‐controllable human Lm γ2 transgene under the cytokeratin 14 promoter on the Lm γ2 knockout background. Mandibles and maxillae from wild‐type and Lm‐332 deficient mice were paraffin‐embedded and sections were immunostained for AMTN, ODAM, or SCPPPQ1. In the maturation stage of amelogenesis, all three proteins localized very discretely in the BL at the ameloblast surface of wild‐type mice. However in Lm‐332 deficient mice, all three proteins accumulated as focal patches within the cell layer rather than at the cell apex. Thus, it is concluded that AMTN, ODAM, and SCPPPQ1 require Lm‐332 for their proper positioning in the BL and for mediating adhesion to the tooth surface. As such, the defects in teeth of patients with junctional epidermolysis bullosa resulting from mutation in Lm‐332 likely reflect altered interactions among these proteins.Grant Funding Source: Supported by CIHR, NIH/NHLBI P01HL029594, Shriners of North America