Mutation of STAT1/3 binding sites in gp130(FXXQ) knock-in mice does not alter hematopoietic stem cell repopulation or self-renewal potential.

Interleukin (IL)-6 family cytokine signaling through gp130 and signal transducer and activator of transcription (STAT) activation is believed important for early hematopoiesis. To determine whether gp130/STAT1/3 physical interaction is required, we compared hematopoietic repopulating activities of embryonic day (E)14.5 fetal liver cells from gp130(FXXQ/FXXQ) knock-in mice, which have four mutated STAT1/3 binding sites. In hematopoietic cells, failure to tyrosine phosphorylate STAT3 by gp130 did not cause any significant effects on myeloid progenitor colony forming units (CFU) in vitro and or on competitive multilineage hematopoietic reconstitution. Serial transplantation of fetal liver (FL) cells was unaffected throughout primary, secondary, and tertiary transplants indicating normal self-renewal capacity. Even gp130(FXXQ/FXXQ) on the background of STAT5 deficiency, with known hematopoietic stem cell (HSC) repopulating dysfunction, did not further impair HSCs beyond that of STAT5 alone. Overall, the defective gp130-mediated STAT1/3 signaling is surprisingly dispensable for HSC function. However, since these mice lack both STAT1/3 binding sites there are several possible explanations for this result and these are discussed.