A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH).

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-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.

• Authors: Jana Pachlopnik Schmid, Chen-Hsuan Ho, Julien Diana, Gérard Pivert, Agnès Lehuen, Frédéric Geissmann, Alain Fischer, Geneviève de Saint Basile
• Journal: European journal of immunology (Eur J Immunol) Vol. 38 Issue 11 Pg. 3219-25 (Nov 2008) ISSN: 0014-2980 [Print] Germany
• PMID: 18991284 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• rab27 GTP-Binding Proteins
• Rab27a protein, mouse
• rab GTP-Binding Proteins

Topics

• Animals
• Disease Models, Animal
• Lymphocytic Choriomeningitis (complications, pathology)
• Lymphohistiocytosis, Hemophagocytic (etiology, pathology)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mutation
• Syndrome
• rab GTP-Binding Proteins (genetics)
• rab27 GTP-Binding Proteins