title: MCPIP1 deficiency in mice results in severe anemia related to autoimmune mechanisms.
abstract: Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1(-/-) developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1(-/-) bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12) deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1(-/-) mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1(-/-) mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1(-/-) mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease.
authors: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors: Zhou
authors: Z
authors: Zhou
authors: Ruidong
authors: R
authors: Miao
authors: Shengping
authors: S
authors: Huang
authors: Brandon
authors: B
authors: Elder
authors: Tim
authors: T
authors: Quinn
authors: Christopher J
authors: CJ
authors: Papasian
authors: Jifeng
authors: J
authors: Zhang
authors: Daping
authors: D
authors: Fan
authors: Y Eugene
authors: YE
authors: Chen
authors: Mingui
authors: M
authors: Fu
mesh_terms: D000740:Anemia / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018798:Anemia, Iron-Deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology; D004920:Erythropoiesis / Q000235:genetics; D005756:Gastritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D056726:Genetic Association Studies; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000473:pathology; D012260:Ribonucleases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014806:Vitamin B 12 Deficiency
chemical_list: D001323:Autoantibodies; D012260:Ribonucleases; C541320:Zc3h12a protein, mouse