Timothy J. Satchwell
Characteristic phenotypes associated with congenital dyserythropoietic anemia (type II) manifest at different stages of erythropoiesis
Satchwell, Timothy J.; Pellegrin, Stephanie; Bianchi, Paola; Hawley, Bethan R.; Gampel, Alexandra; Mordue, Kathryn E.; Budnik, Annika; Fermo, Elisa; Barcellini, Wilma; Stephens, David J.; van den Akker, Emile; Toye, Ashley M.
Authors
Stephanie Pellegrin
Paola Bianchi
Bethan R. Hawley
Alexandra Gampel
Kathryn E. Mordue
Annika Budnik
Elisa Fermo
Wilma Barcellini
David J. Stephens
Emile van den Akker
Ashley M. Toye
Abstract
Congenital dyserythropoietic anemia type II is an autosomally recessive form of hereditary anemia caused by SEC23B gene mutations. Patients exhibit characteristic phenotypes including multinucleate erythroblasts, erythrocytes with hypoglycosylated membrane proteins and an apparent double plasma membrane. Despite ubiquitous expression of SEC23B, the effects of mutations in this gene are confined to the erythroid lineage and the basis of this erythroid specificity remains to be defined. In addition, little is known regarding the stage at which the disparate phenotypes of this disease manifest during erythropoiesis. We employ an in vitro culture system to monitor the appearance of the defining phenotypes associated with congenital dyserythropoietic anemia type II during terminal differentiation of erythroblasts derived from small volumes of patient peripheral blood. Membrane protein hypoglycosylation was detected by the basophilic stage, preceding the onset of multinuclearity in orthochromatic erythroblasts that occurs coincident with the loss of secretory pathway proteins including SEC23A during erythropoiesis. Endoplasmic reticulum remnants were observed in nascent reticulocytes of both diseased and healthy donor cultures but were lost upon further maturation of normal reticulocytes, implicating a defect of ER clearance during reticulocyte maturation in congenital dyserythropoietic anemia type II. We also demonstrate distinct isoform and species-specific expression profiles of SEC23 during terminal erythroid differentiation and identify a prolonged expression of SEC23A in murine erythropoiesis compared to humans. We propose that SEC23A is able to compensate for the absence of SEC23B in mouse erythroblasts, providing a basis for the absence of phenotype within the erythroid lineage of a recently described SEC23B knockout mouse. © 2013 Ferrata Storti Foundation.
Journal Article Type | Article |
---|---|
Online Publication Date | Nov 1, 2013 |
Publication Date | Nov 1, 2013 |
Deposit Date | Jul 11, 2024 |
Publicly Available Date | Jul 12, 2024 |
Journal | Haematologica |
Print ISSN | 0390-6078 |
Electronic ISSN | 1592-8721 |
Publisher | Ferrata Storti Foundation |
Peer Reviewed | Peer Reviewed |
Volume | 98 |
Issue | 11 |
Pages | 1788-1796 |
DOI | https://doi.org/10.3324/haematol.2013.085522 |
Public URL | https://uwe-repository.worktribe.com/output/12121560 |
Files
Characteristic phenotypes associated with congenital dyserythropoietic anemia (type II) manifest at different stages of erythropoiesis
(2.3 Mb)
PDF
Licence
http://creativecommons.org/licenses/by/4.0/
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
You might also like
Complete absence of GLUT1 does not impair human terminal erythroid differentiation
(2024)
Journal Article
Downloadable Citations
About UWE Bristol Research Repository
Administrator e-mail: repository@uwe.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search