期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 38, 期 11, 页码 3219-3225出版社
WILEY
DOI: 10.1002/eji.200838488
关键词
Animal models; Clinical immunology; Cytotoxicity; Immunodeficiencies
类别
资金
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Agence Nationale de la Recherche [ANR-05-MIM-010, BLAN06-3_145379]
- Fondation pour la Recherche Medicale
- European Community [HEALTH-F2-2008-201461]
- Swiss Foundation for Grants in Medicine and Biology [1211/PASMA-110658/1]
- Fondazione Ettore e Valeria Rossi
Griscelli syndrome type 2 is caused by mutations in the RAB27A gene and is a rare and potentially fatal immune disorder associated with hemophagocytic lymphohistiocytosis (HLH). Animal models could provide assistance for better understanding the mechanisms and finding new treatments. Rab27a-deficient (ashen) mice do not spontaneously develop HLH. When injected with lymphocytic choriomeningitis virus (LCMV) strain WE, Rab27a-deficient C57BL/6 mice developed wasting disease, hypothermia, splenomegaly, cytopenia (anemia, neutropenia and thrombocytopenia), hypertriglyceridemia and increased levels of IFN-gamma, TNF-alpha, GM-CSF, IL-12, CCL5 and IL-10. Activated macrophages with hemophagocytosis were found in liver sections of these mice. Compared with perforin-deficient mice, LCMV-infected Rab27a-deficient mice showed a substantially better survival rate and slightly higher viral doses were needed to trigger HLH in Rab27a-deficient mice. This study demonstrates that LCMV-infected Rab27a-deficient C57BL/6 mice develop features consistent with HLH and, therefore, represent a murine model of HLH in human Griscelli syndrome type 2.
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