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Molecular and Cellular Biology, February 2003, p. 1075-1084, Vol. 23, No. 3
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.3.1075-1084.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Essential Role for NFI-C/CTF Transcription-Replication Factor in Tooth Root Development

George Steele-Perkins,1,2 Kenneth G. Butz,1,2 Gary E. Lyons,3 Margarita Zeichner-David,4 Heung-Joong Kim,5 Moon-Il Cho,5 and Richard M. Gronostajski1,2,6*

Lerner Research Institute, Department of Cancer Biology, Cleveland Clinic Foundation,1 Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio,6 Department of Anatomy, University of Wisconsin Medical School, Madison, Wisconsin,3 Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California,4 Department of Oral Biology, School of Dental Medicine,5 Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York2

Received 24 June 2002/ Returned for modification 6 August 2002/ Accepted 7 November 2002

The mammalian tooth forms by a series of reciprocal epithelial-mesenchymal interactions. Although several signaling pathways and transcription factors have been implicated in regulating molar crown development, relatively little is known about the regulation of root development. Four genes encoding nuclear factor I (NFI) transcription-replication proteins are present in the mouse genome: Nfia, Nfib, Nfic, and Nfix. In order to elucidate its physiological role(s), we disrupted the Nfic gene in mice. Heterozygous animals appear normal, whereas Nfic-/- mice have unique tooth pathologies: molars lacking roots, thin and brittle mandibular incisors, and weakened abnormal maxillary incisors. Feeding in Nfic-/- mice is impaired, resulting in severe runting and premature death of mice reared on standard laboratory chow. However, a soft-dough diet mitigates the feeding impairment and maintains viability. Although Nfic is expressed in many organ systems, including the developing tooth, the tooth root development defects were the prominent phenotype. Indeed, molar crown development is normal, and well-nourished Nfic-/- animals are fertile and can live as long as their wild-type littermates. The Nfic mutation is the first mutation described that affects primarily tooth root formation and should greatly aid our understanding of postnatal tooth development.

* Corresponding author. Mailing address: Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 140 Farber Hall, 3435 Main St., Buffalo, NY 14214. Phone: (716) 829-3471. Fax: (716) 829-2725. E-mail: rgron{at}buffalo.edu.

Molecular and Cellular Biology, February 2003, p. 1075-1084, Vol. 23, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.3.1075-1084.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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