Modeling susceptibility versus resistance in allergic airway disease reveals regulation by Tec kinase Itk.
Murine models of allergic asthma have been used to understand the mechanisms of development and pathology in this disease. In addition, knockout mice have contributed significantly to our understanding of the roles of specific molecules and cytokines in these models. However, results can vary significantly depending on the mouse strain used in the model, and in particularly in understanding the effect of specific knockouts. For example, it can be equivocal as to whether specific gene knockouts affect the susceptibility of the mice to developing the disease, or lead to resistance. Here we used a house dust mite model of allergic airway inflammation to examine the response of two strains of mice (C57BL/6 and BALB/c) which differ in their responses in allergic airway inflammation. We demonstrate an algorithm that can facilitate the understanding of the behavior of these models with regards to susceptibility (to allergic airway inflammation) (S(aai)) or resistance (R(aai)) in this model. We verify that both C57BL/6 and BALB/c develop disease, but BALB/c mice have higher S(aai) for development. We then use this approach to show that the absence of the Tec family kinase Itk, which regulates the production of Th2 cytokines, leads to R(aai) in the C57BL/6 background, but decreases S(aai) on the BALB/c background. We suggest that the use of such approaches could clarify the behavior of various knockout mice in modeling allergic asthma.
Sahu
Nisebita
N
Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Morales
J Luis
JL
Fowell
Deborah
D
August
Avery
A
D000465:Algorithms; D000818:Animals; D016535:Bronchial Hyperreactivity; D004198:Disease Susceptibility; D006967:Hypersensitivity / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases