期刊
NATURE IMMUNOLOGY
卷 4, 期 11, 页码 1128-1135出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni983
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- NIAID NIH HHS [AI055001] Funding Source: Medline
- NICHD NIH HHS [HD035920] Funding Source: Medline
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD035920] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI055001] Funding Source: NIH RePORTER
Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1(nu/nu))mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1(Delta), from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1(Delta/Delta) mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1(Delta/Delta) 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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