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Lookup NU author(s): Dr Ralf KistORCiD, Dr Colin Miles, Dr Don Reid, Dr Heiko Peters
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Missing teeth (hypodontia and oligodontia) are a common developmental abnormality in humans and heterozygous mutations of PAX9 have recently been shown to underlie a number of familial, non-syndromic cases. Whereas PAX9 haploinsufficiency has been suggested as the underlying genetic mechanism, it is not known how this affects tooth development. Here we describe a novel, hypomorphic Pax9 mutant allele (Pax9neo) producing decreased levels of Pax9 wild-type mRNA and show that this causes oligodontia in mice. Homozygous Pax9neo mutants (Pax9neo/neo) exhibit hypoplastic or missing lower incisors and third molars, and when combined with the null allele Pax9lacZ, the compound mutants (Pax9neo/lacZ) develop severe forms of oligodontia. The missing molars are arrested at different developmental stages and posterior molars are consistently arrested at an earlier stage, suggesting that a reduction of Pax9 gene dosage affects the dental field as a whole. In addition, hypomorphic Pax9 mutants show defects in enamel formation of the continuously growing incisors, whereas molars exhibit increased attrition and reparative dentin formation. Together, we conclude that changes of Pax9 expression levels have a direct consequence for mammalian dental patterning and that a minimal Pax9 gene dosage is required for normal morphogenesis and differentiation throughout tooth development. © The Author 2005. Published by Oxford University Press. All rights reserved.
Author(s): Kist R, Watson M, Wang X, Cairns P, Miles C, Reid DJ, Peters H
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2005
Volume: 14
Issue: 23
Pages: 3605-3617
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddi388
DOI: 10.1093/hmg/ddi388
PubMed id: 16236760
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