title: Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds.
abstract: WNT10A is a signaling molecule involved in tooth development, and WNT10A defects are associated with tooth agenesis. We characterized Wnt10a null mice generated by the knockout mouse project (KOMP) and six families with WNT10A 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 WNT10A families. WNT10A heterozygotes exhibited molar root taurodontism and mild tooth agenesis (with incomplete penetrance) in their permanent dentitions. Individuals with two defective WNT10A 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 WNT10A 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 WNT10A defects and that the severity of the tooth agenesis correlates with the number of defective WNT10A alleles.
authors: Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University 22 South Avenue Zhongguancun Haidian District, Beijing, 100081, China ; Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: Jie
authors: J
authors: Yang
authors: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: Shih-Kai
authors: SK
authors: Wang
authors: Department of Biomedical Sciences, College of Medicine, Seoul National University 275-1 Yongon-dong, Chongno-gu, Seoul, 110-768, Korea ; Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine 333 Cedar Street, New Haven, Connecticut, 06520.
authors: Murim
authors: M
authors: Choi
authors: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: Bryan M
authors: BM
authors: Reid
authors: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: Yuanyuan
authors: Y
authors: Hu
authors: Graduate Institute of Clinical Dentistry, National Taiwan University No. 1 Chang-Te Street, Taipei, 10048, Taiwan, China.
authors: Yuan-Ling
authors: YL
authors: Lee
authors: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: Curtis R
authors: CR
authors: Herzog
authors: Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, 1011 N. University Ann Arbor, Michigan, 48109-1078.
authors: Hera
authors: H
authors: Kim-Berman
authors: Department of Biomedical Sciences, College of Medicine, Seoul National University 275-1 Yongon-dong, Chongno-gu, Seoul, 110-768, Korea.
authors: Moses
authors: M
authors: Lee
authors: Department of Medical Genetics, Joe DiMaggio Children's Hospital 1150 N. 35th Avenue, Suite 490, Hollywood, Florida, 33021.
authors: Paul J
authors: PJ
authors: Benke
authors: Mouse Biology Program (MBP), University of California 2795 Second Street, Suite 400, Davis, California, 95618.
authors: K C Kent
authors: KC
authors: Lloyd
authors: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: James P
authors: JP
authors: Simmer
authors: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Place, Ann Arbor, Michigan, 48108.
authors: Jan C-C
authors: JC
authors: Hu
keywords: Familial tooth agenesis; hypodontia; oligodontia, taurodontism
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