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Acute Asthma Models to Ovalbumin in the Mouse

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Abstract
Table of Contents
Materials
Figures
Literature Cited

Abstract

Human asthma is defined as a chronic inflammatory disease of the airways. Animal models are required to study asthma pathophysiology and identify and/or evaluate new therapeutic strategies. Several models of asthma have been developed in mice to mimic asthma symptoms, and can be divided in two groups as acute and chronic models. They are characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Several experimental procedures have been implemented, the one mostly used being acute asthma models to ovalbumin. It comprises a sensitization step in the presence of aluminum hydroxide as an adjuvant, and a second step where mice are challenged with the allergen introduced directly into the airways to induce the modeled asthma features. This article describes procedures to efficiently and reproducibly obtain acute asthma features in mice, with ovalbumin as the allergen, which allow group comparisons and/or assessment of the activity of drug candidates. Curr. Protoc. Mouse Biol. 3:31?37 © 2013 by John Wiley & Sons, Inc.

Keywords: asthma; allergy; inflammation; bronchial hyperresponsiveness

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Introduction
Basic Protocol 1: Acute Ovalbumin Asthma Models
Support Protocol 1: Models of Asthma Induced by Ovalbumin
Commentary
Literature Cited
Figures
Tables

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Basic Protocol 1: Acute Ovalbumin Asthma Models Materials

Ovalbumin grade V (Sigma‐Aldrich, cat. no. A5503)
Sterile saline
Aluminum hydroxide (Sigma‐Aldrich, cat. no. 23918‐6)
9‐week‐old male BALB/c or C57BL/6 mice
Anesthetics (50 mg/kg Ketamine/3 mg/kg Xylazine), stored at 4°C

Precision balance (0.1 mg)
50‐ml Falcon tubes
1.5‐ml microtubes, sterile
5 ml sterile culture tubes
15‐ml sterile centrifuge tubes
Rotator mixer
1‐ml sterile syringes
25‐G needles
Vortex mixer
Sterile tips
Precision pipets (20 µl and 1000 µl)
Heating blanket or heating lamp

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Figure 1. Number of eosinophils in bronchoalveolar lavage (BAL) fluid in the 8‐day model with and without aluminum hydroxide. Number of eosinophils in BAL of mice sensitized to OVA in the presence or absence of alum after OVA challenges in the 8‐day hypereosinophilia model. Dots are individuals values and bars are means and SEM values ( n = 10).

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Figure 2. Influence of the quality of aluminum hydroxide on the number of eosinophils in BAL. Number of eosinophils in BAL in ovalbumin‐sensitized and challenged mice in the 8‐day asthma model. Alum 1: mice were sensitized with aluminum hydroxide from Merck (cat. no. 101091); Alum 2: mice were sensitized with aluminum hydroxide from Sigma‐Aldrich (cat. no. 239186). Dots are independent studies ( n = 6 mice/study) and bars are means with SEM values ( n = 6 independent studies).

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Figure 3. Acute asthma models to ovalbumin in mice. Three models of acute asthma composed of sensitization steps with intraperitoneal (i.p.) administration of ovalbumin and aluminum hydroxide, and intranasal (i.n.) challenges with ovalbumin or saline for control mice.

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Figure 4. Measurement of airway resistance in the C57Bl/6 strain of mice in the 21‐day and the 23‐day asthma models. Airway resistance (R) in response to a single dose of aerosolized methacholine (50 mg/kg) was assessed by the Flexivent technique. Blocks are means, and bars are SEM values ( n = 12). *p ≤0.05.

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Literature Cited

Literature Cited
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