title: 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.affiliation: Institut National de la Santé et de la Recherche Médicale U768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Paris, France. jana.pachlopnik@inserm.fr
authors.forename: Jana
authors.initials: J
authors.lastname: Pachlopnik Schmid
authors.forename: Chen-Hsuan
authors.initials: CH
authors.lastname: Ho
authors.forename: Julien
authors.initials: J
authors.lastname: Diana
authors.forename: Gérard
authors.initials: G
authors.lastname: Pivert
authors.forename: Agnès
authors.initials: A
authors.lastname: Lehuen
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000473:pathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation; D013577:Syndrome; D020691:rab GTP-Binding Proteins / Q000235:genetics*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000075745:rab27 GTP-Binding Proteins; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins