Description of the method:
Mouse models of both acute and chronic asthma are available for the investigation of asthma and general lung function. These are mostly based on the sensitization of the animals with ovalbumin (OVA)/alum followed by intranasal allergen provocation and last between 28 days (acute, allergic model) and 70 days (chronic model). Furthermore, lung function can also be analyzed in humanized mice (i.e. immunodeficient animals treated with PBMC from allergic donors) 3 weeks after PBMC transfer. In all models, the immunological basis of the inflammatory processes of asthma and suitable treatment strategies can be investigated.
Using whole body plethysmography the hypersensitivity to the clinically relevant test stimulus methacholine (MCh), which is applied in increasing doses, is measured. The measurement is performed invasively under anesthesia (100 mg/kg ketamine/10-20 mg/kg xylazine/2-3 mg/kg acepromazine). Intubation of the trachea thus enables measurement not only of the upper, but also of the lower airways. Subsequently, the animals must be sacrificed.
For the implementation of the mentioned protocols it is mandatory that the user can present a valid animal experiment application (Tierversuchsantrag) including the approval of lung function measurements, as no lump sum approvals can be granted by the animal protection authority. Experience with tracheotomy/BAL removal or similar surgical procedures should be available. The tolerance of the anaesthetic should be tested in advance. The Asthma Core Facility offers a level S1 safety area in its rooms. The measurement of lung function takes approximately 1 hour per 4 animals.