Defective erythroid maturation in gelsolin mutant mice

BackgroundDuring late differentiation, erythroid cells undergo profound changes involving actin filament remodeling. One of the proteins controlling actin dynamics is gelsolin, a calcium-activated actin filament severing and capping protein. Gelsolin-null (Gsn^−/−) mice generated in a C57BL/6 background are viable and fertile.¹ResultsIn the context of a BALB/c background, the Gsn^−/− mutation causes embryonic death. Gsn^−/− embryos show defective erythroid maturation with persistence of circulating nucleated cells. The few Gsn^−/− mice reaching adulthood fail to recover from phenylhydrazine-induced acute anemia, revealing an impaired response to stress erythropoiesis. In in vitro differentiation assays, E13.5 fetal liver Gsn^−/− cells failed to undergo terminal maturation, a defect partially rescued by Cytochalasin D, and mimicked by administration of Jasplakinolide to the wild-type control samples.ConclusionsIn BALB/c mice, gelsolin deficiency alters the equilibrium between erythrocyte actin polymerization and depolymerization, causing impaired terminal maturation. We suggest a non-redundant role for gelsolin in terminal erythroid differentiation, possibly contributing to the Gsn^−/− mice lethality observed in mid-gestation.