title: Increased red cell turnover in a line of CD22-deficient mice is caused by Gpi1c: a model for hereditary haemolytic anaemia.
abstract: CD22, an inhibitory co-receptor of the BCR, has been identified as a potential candidate gene for the development of autoimmune haemolytic anaemia in mice. In this study, we have examined Cd22(tm1Msn) CD22-deficient mice and identified an increase in RBC turnover and stress erythropoiesis, which might be consistent with haemolysis. 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 autoanti-bodies. 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 haemolytic anaemia in humans.
authors.affiliation: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Walker
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hall
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Kotsopoulou
authors.forename: Marion
authors.initials: M
authors.lastname: Espeli
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.forename: Robert N
authors.initials: RN
authors.lastname: Barker
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000483:Alleles; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology*; D004920:Erythropoiesis / Q000235:genetics / Q000276:immunology; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains; D011110:Polymorphism, Genetic; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000276:immunology
chemical_list: C497868:Cd22 protein, mouse; D016207:Cytokines; D051918:Sialic Acid Binding Ig-like Lectin 2; D005956:Glucose-6-Phosphate Isomerase; C554960:Gpi1 protein, mouse