MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation

Abstract
Matrix metalloproteinase 20 (MMP20) and kallikrein‐related peptidase 4 (KLK4) are secreted proteinases that are essential for proper dental enamel formation. We characterized and compared enamel formed in wild‐type, Mmp20−/−, Klk4−/−, Mmp20+/−Klk4+/−, and Mmp20−/−Klk4−/− mice using dissecting and light microscopy, backscattered scanning electron microscopy (bSEM), SEM, microcomputed tomography (μCT), and energy‐dispersive X‐ray analysis (EDX). Following eruption, fractures were observed on Mmp20−/−, Klk4−/−, Mmp20+/−Klk4+/−, and Mmp20−/−Klk4−/− molars. Failure of the enamel in the Mmp20+/−Klk4+/− molars was unexpected and suggested that digenic effects could contribute to the etiology of amelogenesis imperfecta in humans. Micro‐CT analyses of hemimandibles demonstrated significantly reduced high‐density enamel volume in the Mmp20−/− and Klk4−/− mice relative to the wild‐type, which was further reduced in Mmp20−/−Klk4−/− mice. bSEM images of 7‐week Mmp20−/− and Mmp20−/−Klk4−/− mandibular incisors showed rough, pitted enamel surfaces with numerous indentations and protruding nodules. The Mmp20+/− and Mmp20+/−Klk4+/− incisors showed prominent, evenly spaced, horizontal ridges that were more distinct in Mmp20+/−Klk4+/− incisors relative to Mmp20+/− incisors due to the darkening of the valleys between the ridges. In cross sections, the Mmp20−/− and Mmp20−/−Klk4−...

Source: Molecular Genetics & Genomic Medicine - December 20, 2015 Category: Genetics & Stem Cells Authors: Yuanyuan Hu, Charles E. Smith, Amelia S Richardson, John D. Bartlett, Jan C.C. Hu, James P. Simmer Tags: Original Article Source Type: research