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 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 language | English |
|---|---|
| Pages (from-to) | 980-988 |
| Number of pages | 9 |
| Journal | Haematologica |
| Volume | 97 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 1 2012 |
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Keywords
- Actin dynamics
- Erythroid maturation
- Erythropoiesis
- Gelsolin
ASJC Scopus subject areas
- Hematology
Cite this
Defective erythroid maturation in gelsolin mutant mice. / Cantù, Claudio; Bosè, Francesca; Bianchi, Paola; Reali, Eva; Colzani, Maria Teresa; Cantù, Ileana; Barbarani, Gloria; Ottolenghi, Sergio; Witke, Walter; Spinardi, Laura; Ronchi, Antonella Ellena.
In: Haematologica, Vol. 97, No. 7, 01.07.2012, p. 980-988.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Defective erythroid maturation in gelsolin mutant mice
AU - Cantù, Claudio
AU - Bosè, Francesca
AU - Bianchi, Paola
AU - Reali, Eva
AU - Colzani, Maria Teresa
AU - Cantù, Ileana
AU - Barbarani, Gloria
AU - Ottolenghi, Sergio
AU - Witke, Walter
AU - Spinardi, Laura
AU - Ronchi, Antonella Ellena
PY - 2012/7/1
Y1 - 2012/7/1
N2 - 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.
AB - 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.
KW - Actin dynamics
KW - Erythroid maturation
KW - Erythropoiesis
KW - Gelsolin
UR - http://www.scopus.com/inward/record.url?scp=84863917151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863917151&partnerID=8YFLogxK
U2 - 10.3324/haematol.2011.052522
DO - 10.3324/haematol.2011.052522
M3 - Article
C2 - 22271892
AN - SCOPUS:84863917151
VL - 97
SP - 980
EP - 988
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 7
ER -