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Journal of Histochemistry and Cytochemistry
Volume 52 (1): 131-140, 2004
Copyright ©The Histochemical Society, Inc.

Phenotypic Changes in Dentition of Runx2 Homozygote-null Mutant Mice

Thomas Åberg, Adriana Cavender, Joel S. Gaikwad, Antonius L.J.J. Bronckers, Xiuping Wang, Janna Waltimo–Sirén, Irma Thesleff and Rena N. D'Souza

Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Finland (TÅ,XW,JW–S,IT); Department of Orthodontics, University of Texas Health Science Center, Houston, Texas (AC,JSG,RND); and Department of Oral Cell Biology, ACTA, Amsterdam, The Netherlands (ALJJB)

Correspondence to: Rena N. D'Souza, DDS, PhD, Dept. of Orthodontics, Dental Branch, Room 365, U. of Texas Health Science Center, 6516 MD Anderson Boulevard, Houston, TX 77030. E-mail: Rena.N.DSouza{at}uth.tmc.edu

Genetic and molecular studies in humans and mice indicate that Runx2 (Cbfa1) is a critical transcriptional regulator of bone and tooth formation. Heterozygous mutations in Runx2 cause cleidocranial dysplasia (CCD), an inherited disorder in humans and mice characterized by skeletal defects, supernumerary teeth, and delayed eruption. Mice lacking the Runx2 gene die at birth and lack bone and tooth development. Our extended phenotypic studies of Runx2 mutants showed that developing teeth fail to advance beyond the bud stage and that mandibular molar organs were more severely affected than maxillary molar organs. Runx2 (-/-) tooth organs, when transplanted beneath the kidney capsules of nude mice, failed to progress in development. Tooth epithelial–mesenchymal recombinations using Runx2 (+/+) and (-/-) tissues indicate that the defect in mesenchyme cannot be rescued by normal dental epithelium. Finally, our molecular analyses showed differential effects of the absence of Runx2 on tooth extracellular matrix (ECM) gene expression. These data support the hypothesis that Runx2 is one of the key mesenchymal factors that influences tooth morphogenesis and the subsequent differentiation of ameloblasts and odontoblasts. (J Histochem Cytochem 52:131–139, 2004)

Key Words: Runx2 • odontogenesis • knockout mice • phenotypic analysis • epithelial–mesenchymal interactions • matrix gene expression • cleft palate • eyelid opening


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