title: Defective erythroid maturation in gelsolin mutant mice.
abstract: 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
  
  
  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.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università Milano-Bicocca, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cantù
authors.forename: Francesca
authors.initials: F
authors.lastname: Bosè
authors.forename: Paola
authors.initials: P
authors.lastname: Bianchi
authors.forename: Eva
authors.initials: E
authors.lastname: Reali
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Colzani
authors.forename: Ileana
authors.initials: I
authors.lastname: Cantù
authors.forename: Gloria
authors.initials: G
authors.lastname: Barbarani
authors.forename: Sergio
authors.initials: S
authors.lastname: Ottolenghi
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
authors.forename: Laura
authors.initials: L
authors.lastname: Spinardi
authors.forename: Antonella Ellena
authors.initials: AE
authors.lastname: Ronchi
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000740:Anemia / Q000139:chemically induced; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D047630:Depsipeptides / Q000494:pharmacology; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004920:Erythropoiesis / Q000235:genetics*; D005333:Fetus; D018260:Gelsolin / Q000172:deficiency / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010659:Phenylhydrazines / Q000633:toxicity
chemical_list: D000199:Actins; D015415:Biomarkers; D047630:Depsipeptides; D018260:Gelsolin; D010659:Phenylhydrazines; C030299:phenylhydrazine; C057531:jasplakinolide; D015638:Cytochalasin D