| First Author | Kreder D | Year | 1999 |
| Journal | EMBO J | Volume | 18 |
| Issue | 9 | Pages | 2472-9 |
| PubMed ID | 10228161 | Mgi Jnum | J:54972 |
| Mgi Id | MGI:1336835 | Doi | 10.1093/emboj/18.9.2472 |
| Citation | Kreder D, et al. (1999) Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice. EMBO J 18(9):2472-9 |
| abstractText | The WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N- SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt phenotypic abnormalities; in particular, the architecture and cellular composition of lymphoid organs appeared to be unaltered. An essential role of FAN in the TNF-induced activation of N-SMase was demonstrated using thymocytes from FAN knockout mice. Activation of extracellular signal-regulated kinases in response to TNF treatment, however, was not impaired by the absence of the FAN protein. FAN-deficient mice show delayed kinetics of recovery after cutaneous barrier disruption suggesting a physiological role of FAN in epidermal barrier repair. Although FAN exhibits striking structural homologies with the CHS/Beige proteins, FAN-deficient mice did not reproduce the phenotype of beige mice. |
