Open AccessTaurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds
Author(s) -
Yang Jie,
Wang ShihKai,
Choi Murim,
Reid Bryan M.,
Hu Yuanyuan,
Lee YuanLing,
Herzog Curtis R.,
KimBerman Hera,
Lee Moses,
Benke Paul J.,
Kent Lloyd K. C.,
Simmer James P.,
Hu Jan C.C.
Publication year - 2015
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.111
Subject(s) - molar , null allele , biology , penetrance , hypodontia , medicine , axin2 , phenotype , genetics , dentistry , wnt signaling pathway , gene
WNT 10A is a signaling molecule involved in tooth development, and WNT 10A defects are associated with tooth agenesis. We characterized Wnt10a null mice generated by the knockout mouse project ( KOMP ) and six families with WNT 10A mutations, including a novel p.Arg104Cys defect, in the absence of EDA , EDAR , or EDARADD variations. Wnt10a null mice exhibited supernumerary mandibular fourth molars, and smaller molars with abnormal cusp patterning and root taurodontism. Wnt10a −/− incisors showed distinctive apical–lingual wedge‐shaped defects. These findings spurred us to closely examine the dental phenotypes of our WNT 10A families. WNT 10A heterozygotes exhibited molar root taurodontism and mild tooth agenesis (with incomplete penetrance) in their permanent dentitions. Individuals with two defective WNT 10A alleles showed severe tooth agenesis and had fewer cusps on their molars. The misshapened molar crowns and roots were consistent with the Wnt10a null phenotype and were not previously associated with WNT 10A defects. The missing teeth contrasted with the presence of supplemental teeth in the Wnt10a null mice and demonstrated mammalian species differences in the roles of Wnt signaling in early tooth development. We conclude that molar crown and root dysmorphologies are caused by WNT 10A defects and that the severity of the tooth agenesis correlates with the number of defective WNT 10A alleles.