| First Author | Mélet F | Year | 1996 |
| Journal | Mol Cell Biol | Volume | 16 |
| Issue | 6 | Pages | 2708-18 |
| PubMed ID | 8649378 | Mgi Jnum | J:33052 |
| Mgi Id | MGI:80539 | Doi | 10.1128/mcb.16.6.2708 |
| Citation | Melet F, et al. (1996) Generation of a novel Fli-1 protein by gene targeting leads to a defect in thymus development and a delay in Friend virus-induced erythroleukemia. Mol Cell Biol 16(6):2708-18 |
| abstractText | The proto-oncogene Fli-1 is a member of the ets family of transcription factor genes, Its activation by either chromosomal translocation or proviral insertion leads to Ewing's sarcoma in humans or erythroleukemia in mice, respectively, Fli-1 is preferentially expressed in hematopoietic and endothelial cells, This expression pattern resembled that of c-ets-1, another ets gene closely related and physically linked to Fli-1, We also generated a germ line mutation in Fli-1 by homologous recombination in embryonic stem cells, Homozygous mutant mice exhibit thymic hypocellularity which is not related to a defect in a specific subpopulation of thymocytes or to increased apoptosis, suggesting that Fli-1 is an important regulator of a prethymic T-cell progenitor, This thymus phenotype was corrected by crossing the Fli-1- deficient mice with transgenic mice expressing Fli-1 cDNA, Homozygous mutant mice remained susceptible to erythroleukemia induction by Friend murine leukemia virus, although the latency period was significantly increased, Surprisingly, the mutant Fli-1 allele was still a target for Friend murine leukemia virus integration, and leukemic spleens with a rearranged Fli-1 gene expressed a truncated Fli-1 protein that appears to arise from an internal translation initiation site and alternative splicing around the neo cassette used in the gene targeting, The fortuitous discovery of the mutant Fli-1 protein, revealed only as the result of the clonal expansion of leukemic cells harboring a rearranged Fli-1 gene; suggests caution in the interpretation of gene-targeting experiments that result in either no or only a subtle phenotypic alteration. |
