Nature Immunology4, 1128 - 1135 (2003)
Published online: 5 October 2003; | doi:10.1038/ni983
A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation
Dong-ming Su1, Samuel Navarre2, Won-jong Oh2, Brian G Condie1
& Nancy R Manley1
1
Department of Genetics, Life Sciences Building, University of Georgia, Athens, Georgia 30602, USA.
2
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Correspondence should be addressed to Nancy R Manley nmanley@uga.edu
Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1nu/nu) mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1, from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1/ mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1/ thymus promoted T cell development, but with specific defects at both the double-negative and double-positive stages. Thus, initiation and progression of TEC differentiation are genetically separable functions of Foxn1, and the N-terminal domain is required for crosstalk-dependent TEC differentiation.
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