In:
European Journal of Immunology, Wiley, Vol. 38, No. 11 ( 2008-11), p. 3219-3225
Abstract:
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‐γ, TNF‐α, 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.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.200838488
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
1491907-2