title: Absence of a red blood cell phenotype in mice with hematopoietic deficiency of SEC23B.
abstract: Congenital dyserythropoietic anemia type II (CDAII) is an autosomal recessive disease of ineffective erythropoiesis characterized by increased bi/multinucleated erythroid precursors in the bone marrow. CDAII results from mutations in SEC23B. The SEC23 protein is a core component of coat protein complex II-coated vesicles, which transport secretory proteins from the endoplasmic reticulum to the Golgi apparatus. Though the genetic defect underlying CDAII has been identified, the pathophysiology of this disease remains unknown. We previously reported that SEC23B-deficient mice die perinatally, exhibiting massive pancreatic degeneration, with this early mortality limiting evaluation of the adult hematopoietic compartment. We now report that mice with SEC23B deficiency restricted to the hematopoietic compartment survive normally and do not exhibit anemia or other CDAII characteristics. We also demonstrate that SEC23B-deficient hematopoietic stem cells (HSC) do not exhibit a disadvantage at reconstituting hematopoiesis when compared directly to wild-type HSC in a competitive repopulation assay. Secondary bone marrow transplants demonstrated continued equivalence of SEC23B-deficient and WT HSC in their hematopoietic reconstitution potential. The surprising discordance in phenotypes between SEC23B-deficient mice and humans may reflect an evolutionary shift in SEC23 paralog function and/or expression, or a change in a specific COPII cargo critical for erythropoiesis.
authors: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors: Rami
authors: R
authors: Khoriaty
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Matthew P
authors: MP
authors: Vasievich
authors: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: Morgan
authors: M
authors: Jones
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Lesley
authors: L
authors: Everett
authors: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: Jennifer
authors: J
authors: Chase
authors: Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors: Jiayi
authors: J
authors: Tao
authors: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: David
authors: D
authors: Siemieniak
authors: Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors: Bin
authors: B
authors: Zhang
authors: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: Ivan
authors: I
authors: Maillard
authors: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA ginsburg@umich.edu.
authors: David
authors: D
authors: Ginsburg
mesh_terms: D000742:Anemia, Dyserythropoietic, Congenital / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000473:pathology*; D004920:Erythropoiesis / Q000235:genetics; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D033921:Vesicular Transport Proteins / Q000097:blood* / Q000235:genetics* / Q000378:metabolism
chemical_list: C575519:SEC23B protein, mouse; C079038:Sec23a protein, mouse; D033921:Vesicular Transport Proteins