Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies using MCP-induced protein 1 (MCPIP1)/Zc3h12a-deficient mice suggest that MCPIP1 is an important regulator of inflammation and immune homeostasis. However, the characterization of the immunological phenotype of MCPIP1-deficient mice has not been detailed. In this study, we performed evaluation through histological, flow cytometric, enzyme-linked immunosorbent assay and real-time PCR analysis and found that targeted disruption of MCPIP1 gene leads to fatal, highly aggressive and widespread immune-related lesions. In addition to previously observed growth retardation, splenomegaly, lymphoadenopathy, severe anemia and premature death, MCPIP1-deficient mice showed disorganization of lymphoid organs, including spleen, lymph nodes and thymus, and massive infiltration of lymphocytes, macrophages and neutrophils into many other non-lymphoid organs, primarily in lungs and liver. Flow cytometric analysis found significant increase in activated and differentiated T cells in peripheral blood and spleen of MCPIP1-deficient mice. Moreover, heightened production of inflammatory cytokines from activated macrophages and T cells were observed in MCPIP1-deficient mice. Interestingly, treatment of MCPIP1-deficient mice with antibiotics resulted in significant improvement of life span and a decrease in inflammatory syndrome. Taken together, these results suggest a prominent role for MCPIP1 in the control of inflammation and immune homeostasis.
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PMID:Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease. 2362 3

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.
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PMID:MCPIP1 deficiency in mice results in severe anemia related to autoimmune mechanisms. 2432 5