Increased susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis
1 Division of Biochemistry, National Institute of Siddha, Chennai, India
2 Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, 45229-3039, USA
3 Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, 45229-3039, USA
4 Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, 45229-3039, USA
5 Department of Molecular and Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, 45267, USA
BMC Immunology 2011, 12:14 doi:10.1186/1471-2172-12-14Published: 3 February 2011
Experimental analyses have identified strain-dependent factors that regulate susceptibility to anaphylaxis in mice. We assessed the susceptibility of the widely used 129SvEvBrd (also known as 129S5) mouse strain to IgE/mast cell-mediated anaphylaxis as compared to BALB/c. Mice were subjected to passive and oral Ovalbumin [OVA]-induced active anaphylaxis. Tissue mast cell, plasma histamine, total IgE and OVA-specific IgE levels and susceptibility to histamine i.v infusion were assessed. Bone marrow mast cell (BMMC)s were examined for FcεRI, c-kit, degranulation efficiency, proliferation, apoptosis and cytokine profile.
129S5 mice had significantly increased susceptibility to passive and oral OVA-induced active anaphylaxis. Increased susceptibility to anaphylaxis was associated with increased homeostatic mast cell levels but not OVA-specific IgE or IgG1 levels. In vitro analyses of BMMCs revealed no difference in FcεRI and c-Kit expression, however, 129S5 BMMCs possessed greater proliferative capacity and reduced caspase-3-mediated apoptosis. IgE-BMMC degranulation assays demonstrated no difference in degranulation efficiency. Furthermore, 129S5 mice possessed increased sensitivity to histamine-induced hypothermia.
We conclude that 129S5 mice have increased susceptibility to anaphylaxis as compared to BALB/c strain and their increased susceptibility was associated with altered mast cell proliferation and homeostatic tissue levels and responsiveness to histamine. Given the wide spread usage of the 129SvEvBrd strain of mice in experimental gene targeting methodology, these data have important implications for studying IgE-reactions in mouse systems.