| First Author | Ordoñez-Rueda D | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 9 | Pages | 2395-408 |
| PubMed ID | 22684987 | Mgi Jnum | J:187946 |
| Mgi Id | MGI:5438764 | Doi | 10.1002/eji.201242589 |
| Citation | Ordonez-Rueda D, et al. (2012) A hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia. Eur J Immunol 42(9):2395-408 |
| abstractText | Using N-ethyl-N-nitrosourea-induced mutagenesis, we established a mouse model with a novel form of neutropenia resulting from a point mutation in the transcriptional repressor Growth Factor Independence 1 (Gfi1). These mice, called Genista, had normal viability and no weight loss, in contrast to mice expressing null alleles of the Gfi1 gene. Furthermore, the Genista mutation had a very limited impact on lymphopoiesis or on T- and B-cell function. Within the bone marrow (BM), the Genista mutation resulted in a slight increase of monopoiesis and in a block of terminal granulopoiesis. This block occurred just after the metamyelocytic stage and resulted in the generation of small numbers of atypical CD11b(+) Ly-6G(int) neutrophils, the nuclear morphology of which resembled that of mature WT neutrophils. Unexpectedly, once released from the BM, these atypical neutrophils contributed to induce mild forms of autoantibody-induced arthritis and of immune complex-mediated lung alveolitis. They additionally failed to provide resistance to acute bacterial infection. Our study demonstrates that a hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia characterized by a split pattern of functional responses, reflecting the distinct thresholds required for eliciting neutrophil-mediated inflammatory and anti-infectious responses. |
