An Interaction Between Genetic Factors and Gender Determines the Magnitude of the Inflammatory Response in the Mouse Air
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An Interaction Between Genetic Factors and Gender Determines the Magnitude of the Inflammatory Response in the Mouse Air Pouch Model of Acute Inflammation David L. Delano,1 M. Carmen Montesinos,1 Peter D’Eustachio,1 Tim Wiltshire,2 and Bruce N. Cronstein1,3
Abstract—The widely used mouse air pouch model of acute inflammation is inducible in a variety of inbred strains, but the potential influence of genetic background and gender on inflammation severity has never been examined. We directly compared the degree of inflammation induced in the air pouch model across four commonly utilized inbred strains in both male and female mice. We then applied an in silico mapping method to identify loci potentially associated with determining inflammation severity for each gender. Air pouches were induced by subcutaneous injection 3 (3 cc) and 5 (1.5 cc) days prior to the experiment. 4h after carrageenan injection, exudates were retrieved and leukocyte concentration quantified using a hemocytometer. The in silico mapping method was applied as described below. The strain order for mean leukocyte count/mL in inflamed exudates differed between genders. In males, the order was C57BL/6J > BALB/cByJ > DBA/2J > DBA/1J, while in females the order was BALB/cByJ > DBA/2J > C57BL/6J > DBA/1J. The difference in inflammation severity between genders reached significance only in C57BL/6J mice. Independent in silico analysis based on phenotypic data from male versus female mice identified distinct sets of loci as potentially associated with the exudate count reached. We conclude that the degree of inflammation induced in the mouse air pouch model of inflammation is strain-specific and, therefore, genetically based, and the pattern of interstrain differences is altered in male relative to female mice. The loci identified by in silico mapping likely contain genes with differential roles in determining this phenotype between genders. KEY WORDS: QTL; in silico mapping; genomics.
INTRODUCTION
in a variety of strains, a trait not shared by other models such as collagen induced arthritis, which may only be applied in a few strains [7–11]. This limitation precludes its use when flexibility in strain choice is limited, as is often the case with knockout or disease-susceptibility strains. Recently, strain-specific [7, 12–16] and gender-specific [15, 17, 18] differences in severity have been reported in a number of murine models of inflammation. Such findings have direct implications on the design and interpretation of experiments, and may also prove useful for investigating the nature of similar phenomena observed in patients. For example, women are more commonly affected by many autoimmune diseases including
The air pouch model of acute inflammation has been widely used over the last 30 years as a means of testing the efficacy of anti-inflammatory drugs, identifying factors involved in inflammation and in numerous other applications [1–6]. Its value lies in part in its inducibility 1 New
York University Medical Center, New York, New York. Institute
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