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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia.

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.[1]


  1. Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia. Kist, R., Watson, M., Wang, X., Cairns, P., Miles, C., Reid, D.J., Peters, H. Hum. Mol. Genet. (2005) [Pubmed]
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