Affordable Access

deepdyve-link
Publisher Website

Ablation of Tmcc2 Gene Impairs Erythropoiesis in Mice.

Authors
  • Kumari, Ranju1, 2
  • Grzywa, Tomasz M3, 4, 5
  • Małecka-Giełdowska, Milena6
  • Tyszkowska, Karolina7
  • Wrzesień, Robert7
  • Ciepiela, Olga6
  • Nowis, Dominika3, 5
  • Kaźmierczak, Piotr1
  • 1 Centre of New Technologies, University of Warsaw, Banacha 2C, 02-097 Warsaw, Poland. , (Poland)
  • 2 School of Molecular Medicine, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland. , (Poland)
  • 3 Department of Immunology, Medical University of Warsaw, Nielubowicza 5, 02-097 Warsaw, Poland. , (Poland)
  • 4 Doctoral School, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland. , (Poland)
  • 5 Laboratory of Experimental Medicine, Medical University of Warsaw, Nielubowicza 5, 02-097 Warsaw, Poland. , (Poland)
  • 6 Department of Laboratory Medicine, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland. , (Poland)
  • 7 Central Laboratory of Experimental Animal, Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland. , (Poland)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
May 09, 2022
Volume
23
Issue
9
Identifiers
DOI: 10.3390/ijms23095263
PMID: 35563652
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

(1) Background: Transcriptomic and proteomic studies provide a wealth of new genes potentially involved in red blood cell (RBC) maturation or implicated in the pathogenesis of anemias, necessitating validation of candidate genes in vivo; (2) Methods: We inactivated one such candidate, transmembrane and coiled-coil domain 2 (Tmcc2) in mice, and analyzed the erythropoietic phenotype by light microscopy, transmission electron microscopy (TEM), and flow cytometry of erythrocytes and erythroid precursors; (3) Results: Tmcc2-/- pups presented pallor and reduced body weight due to the profound neonatal macrocytic anemia with numerous nucleated RBCs (nRBCs) and occasional multinucleated RBCs. Tmcc2-/- nRBCs had cytoplasmic intrusions into the nucleus and double membranes. Significantly fewer erythroid cells were enucleated. Adult knockouts were normocytic, mildly polycythemic, with active extramedullary erythropoiesis in the spleen. Altered relative content of different stage CD71+TER119+ erythroid precursors in the bone marrow indicated a severe defect of erythroid maturation at the polychromatic to orthochromatic transition stage; (4) Conclusions: Tmcc2 is required for normal erythropoiesis in mice. While several phenotypic features resemble congenital dyserythropoietic anemias (CDA) types II, III, and IV, the involvement of TMCC2 in the pathogenesis of CDA in humans remains to be determined.

Report this publication

Statistics

Seen <100 times