Defective erythroid maturation in gelsolin mutant mice

Claudio Cantù, Francesca Bosè, Paola Bianchi, Eva Reali, Maria Teresa Colzani, Ileana Cantù, Gloria Barbarani, Sergio Ottolenghi, Walter Witke, Laura Spinardi, Antonella Ellena Ronchi

Research output: Contribution to journalArticlepeer-review


Background During 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.1 Design and Methods We analyzed the functional roles of gelsolin in erythropoiesis by: (i) evaluating gelsolin expression in murine fetal liver cells at different stages of erythroid differentiation (using reverse transcription polymerase chain reaction analysis and immunohistochemistry), and (ii) characterizing embryonic and adult erythropoiesis in Gsn-/- BALB/c mice (morphology and erythroid cultures). Results In 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. Conclusions In 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.

Original languageEnglish
Pages (from-to)980-988
Number of pages9
Issue number7
Publication statusPublished - Jul 1 2012


  • Actin dynamics
  • Erythroid maturation
  • Erythropoiesis
  • Gelsolin

ASJC Scopus subject areas

  • Hematology


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