Hypomaturation Enamel Defects in Klk4 Knockout/LacZ Knockin Mice
Open Access
- 1 July 2009
- journal article
- Published by Elsevier BV
- Vol. 284 (28), 19110-19121
- https://doi.org/10.1074/jbc.m109.013623
Abstract
Kallikrein 4 (Klk4) is believed to play an essential role in enamel biomineralization, because defects in KLK4 cause hypomaturation amelogenesis imperfecta. We used gene targeting to generate a knockin mouse that replaces the Klk4 gene sequence, starting at the translation initiation site, with a lacZ reporter gene. Correct targeting of the transgene was confirmed by Southern blot and PCR analyses. Histochemical X-gal (5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside) staining demonstrated expression of beta-galactosidase in maturation stage ameloblasts. No X-gal staining was observed in secretory stage ameloblasts or in odontoblasts. Retained enamel proteins were observed in the maturation stage enamel of the Klk4 null mouse, but not in the Klk4 heterozygous or wild-type mice. The enamel layer in the Klk4 null mouse was normal in thickness and contained decussating enamel rods but was rapidly abraded following weaning, despite the mice being maintained on soft chow. In function the enamel readily fractured within the initial rod and interrod enamel above the parallel enamel covering the dentino-enamel junction. Despite the lack of Klk4 and the retention of enamel proteins, significant levels of crystal maturation occurred (although delayed), and the enamel achieved a mineral density in some places greater than that detected in bone and dentin. An important finding was that individual enamel crystallites of erupted teeth failed to grow together, interlock, and function as a unit. Instead, individual crystallites seemed to spill out of the enamel when fractured. These results demonstrate that Klk4 is essential for the removal of enamel proteins and the proper maturation of enamel crystals.Keywords
This publication has 84 references indexed in Scilit:
- Specific increase of human kallikrein 4 mRNA and protein levels in breast cancer stromal cellsBiochemical and Biophysical Research Communications, 2008
- Enamel Defects and Ameloblast-specific Expression in Enam Knock-out/lacZ Knock-in MicePublished by Elsevier BV ,2008
- The anion exchanger Ae2 is required for enamel maturation in mouse teethMatrix Biology, 2008
- Morphological and Molecular Evidence for a Stepwise Evolutionary Transition from Teeth to Baleen in Mysticete WhalesSystematic Biology, 2008
- Hen's teeth with enamel cap: from dream to impossibilityBMC Evolutionary Biology, 2008
- Kallikrein 4 Is a Proliferative Factor that Is Overexpressed in Prostate CancerCancer Research, 2007
- Three‐Dimensional Micro‐Computed Tomographic Imaging of Alveolar Bone in Experimental Bone Loss or RepairThe Journal of Periodontology, 2007
- Molecular cloning and mRNA tissue distribution of a novel matrix metalloproteinase isolated from porcine enamel organGene, 1996
- Epitaxial overgrowth of apatite crystals on the thin-ribbon precursor at early stages of porcine enamel mineralizationCalcified Tissue International, 1993
- DNA sequence for cloned cDNA for murine amelogenin reveal the amino acid sequence for enamel-specific proteinBiochemical and Biophysical Research Communications, 1985