Defective Erythroid Maturation In Gelsolin Mutant MiceShow others and affiliations
2012 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 7, p. 980-988Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Pavia, Italy: Fondazione Ferrata Storti , 2012. Vol. 97, no 7, p. 980-988
Keywords [en]
erythropoiesis, erythroid maturation, actin dynamics, gelsolin
National Category
Hematology
Identifiers
URN: urn:nbn:se:liu:diva-150045DOI: 10.3324/haematol.2011.052522ISI: 000308446600005PubMedID: 22271892Scopus ID: 2-s2.0-84863917151OAI: oai:DiVA.org:liu-150045DiVA, id: diva2:1237350
2018-08-082018-08-082021-03-23Bibliographically approved