Increased red cell turnover in a line of CD22-deficient mice is caused by Gpi1(c): A model for hereditary hemolytic anemia

Jennifer A Walker, Andrew M Hall, Ekaterini Kotsopoulou, Marion Espeli, Lars Nitschke, Robert N Barker, Paul A Lyons, Kenneth G C Smith

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Abstract

CD22, an inhibitory co-receptor of the B-cell receptor, has been identified as a potential candidate gene for the development of autoimmune hemolytic anemia in mice. In this study, we have examined Cd22(tm1Msn) CD22-deficient mice and identified an increase in red blood cell (RBC) turnover and stress erythropoiesis, which might be consistent with hemolysis. We then, however, eliminated CD22-deficiency as the cause of accelerated RBC turnover and established that enhanced RBC turnover occurs independently of B cells and anti-RBC autoantibodies. Accelerated RBC turnover in this particular strain of CD22-deficient mice is red cell intrinsic and appears to be the consequence of a defective allele of glucose phosphate isomerase, Gpi1(c) . This form of Gpi1 was originally derived from wild mice and results in a substantial reduction in enzyme activity. We have identified the polymorphism that causes impaired catalytic activity in the Gpi1(c) allele, and biochemically confirmed an approximate 75% reduction of GPI1 activity in Cd22(-/-) RBCs. The Cd22(-/-) .Gpi1(c) congenic mouse provides a novel animal model of GPI1-deficiency, which is one of the most common causes of chronic non-spherocytic hemolytic anemia in humans.
Original languageEnglish
Pages (from-to)3212-3222
Number of pages11
JournalEuropean Journal of Immunology
Volume42
Issue number12
Early online date16 Oct 2012
DOIs
Publication statusPublished - Dec 2012

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Keywords

  • anaemia
  • CD22
  • erythrocytes
  • glucose-6-phosphate isomerase
  • polymorphism

Cite this

Walker, J. A., Hall, A. M., Kotsopoulou, E., Espeli, M., Nitschke, L., Barker, R. N., Lyons, P. A., & Smith, K. G. C. (2012). Increased red cell turnover in a line of CD22-deficient mice is caused by Gpi1(c): A model for hereditary hemolytic anemia. European Journal of Immunology, 42(12), 3212-3222. https://doi.org/10.1002/eji.201242633