| First Author | Sun L | Year | 2010 |
| Journal | Aging Cell | Volume | 9 |
| Issue | 3 | Pages | 347-57 |
| PubMed ID | 20156205 | Mgi Jnum | J:216122 |
| Mgi Id | MGI:5607720 | Doi | 10.1111/j.1474-9726.2010.00559.x |
| Citation | Sun L, et al. (2010) Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution. Aging Cell 9(3):347-57 |
| abstractText | Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or nonhematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle because of the shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreER(T) (uCreER(T)) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreER(T)-fx/fx mice showed an accelerated age-related thymic involution owing to progressive loss of FoxN1(+) TECs. The thymic aging phenotypes were clearly observable as early as at 3-6 months of age, resembling the naturally aged (18-22-month-old) murine thymus. By intrathymically supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and defective peripheral CD4(+) T-cell function could be partially rescued. The results support the notion that decline of a single epithelial cell-autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age-related thymic involution in mice. |
