Hematopoietic overexpression of FOG1 does not affect B-cells but reduces the number of circulating eosinophils

FOG1 的造血过度表达不会影响 B 细胞,但会减少循环嗜酸性粒细胞的数量

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作者:Camille Du Roure, Aude Versavel, Thierry Doll, Chun Cao, Vincent Pillonel, Gabriele Matthias, Markus Kaller, Jean-François Spetz, Patrick Kopp, Hubertus Kohler, Matthias Müller, Patrick Matthias

Abstract

We have identified expression of the gene encoding the transcriptional coactivator FOG-1 (Friend of GATA-1; Zfpm1, Zinc finger protein multitype 1) in B lymphocytes. We found that FOG-1 expression is directly or indirectly dependent on the B cell-specific coactivator OBF-1 and that it is modulated during B cell development: expression is observed in early but not in late stages of B cell development. To directly test in vivo the role of FOG-1 in B lymphocytes, we developed a novel embryonic stem cell recombination system. For this, we combined homologous recombination with the FLP recombinase activity to rapidly generate embryonic stem cell lines carrying a Cre-inducible transgene at the Rosa26 locus. Using this system, we successfully generated transgenic mice where FOG-1 is conditionally overexpressed in mature B-cells or in the entire hematopoietic system. While overexpression of FOG-1 in B cells did not significantly affect B cell development or function, we found that enforced expression of FOG-1 throughout all hematopoietic lineages led to a reduction in the number of circulating eosinophils, confirming and extending to mammals the known function of FOG-1 in this lineage.

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