title: Hematopoietic overexpression of FOG1 does not affect B-cells but reduces the number of circulating eosinophils.
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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Camille
authors.initials: C
authors.lastname: Du Roure
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; Faculty of Sciences, University of Basel, Basel, Switzerland.
authors.forename: Aude
authors.initials: A
authors.lastname: Versavel
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Doll
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Chun
authors.initials: C
authors.lastname: Cao
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; Faculty of Sciences, University of Basel, Basel, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pillonel
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Matthias
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Kaller
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Spetz
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kopp
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Kohler
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; Faculty of Sciences, University of Basel, Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001772:Blood Cell Count; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci / Q000235:genetics; D006410:Hematopoiesis; D006801:Humans; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse
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