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Defective Erythroid...
Defective Erythroid Maturation In Gelsolin Mutant Mice
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- Cantù, Claudio (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy
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- Bosè, Francesca (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy / Department of Immunology, INGM-National Institute of Molecular Genetics, Milan, Italy
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- Bianchi, Paola (author)
- Haematology Unit 2, Unit of Physiopathology of Anaemia, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Milan, Italy
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- Reali, Eva (author)
- Department of Immunology, INGM-National Institute of Molecular Genetics, Milan, Italy
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- Colzani, Maria Teresa (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy
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- Cantù, Ileana (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy
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- Barbarani, Gloria (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy
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- Ottolenghi, Sergio (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy
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- Witke, Walter (author)
- Institut of Genetics, University of Bonn, Bonn, Germany
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- Spinardi, Laura (author)
- Scientific Direction, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Milan, Italy
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- Ronchi, Antonella Ellena (author)
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan Italy
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(creator_code:org_t)
- 2012-01-22
- 2012
- English.
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In: Haematologica. - Pavia, Italy : Fondazione Ferrata Storti. - 0390-6078 .- 1592-8721. ; 97:7, s. 980-988
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Abstract
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- 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.1DESIGN 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- erythropoiesis
- erythroid maturation
- actin dynamics
- gelsolin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Cantù, Claudio
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Bosè, Francesca
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Bianchi, Paola
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Reali, Eva
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Colzani, Maria T ...
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Cantù, Ileana
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Barbarani, Glori ...
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Ottolenghi, Serg ...
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Witke, Walter
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Spinardi, Laura
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Ronchi, Antonell ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Haematologica
- By the university
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Linköping University