Ovalbumin induced allergic asthma in huNSG mice

Species

Mouse

Field of application:

Highly immunodeficient new born NSG mice become humanized by transplantation of hematopoietic stem cells. Within 10 weeks a complete human immune system develops. At the age of 15 weeks allergic asthma can be induced in humanized mice by repeated systemic injection of ovalbumin together with an adjuvant followed by daily challenge of the respiratory tract with the allergen. After 10 days of challenge mice develop clinical symptoms of allergic asthma.

The model offers the opportunity to test new therapeutics for allergic asthma directly in human immune systems. It can be used for the following fields of application:

  • Pharmacodynamics and pharmacokinetics
  • (Patho)physiological processes
  • Therapeutic efficacy
  • Proof of concept

Endpoints/Outcome parameter

  • Dynamic compliance, Lung resistance, Enhanced pause (lung function measurement; in vivo)
  • immune cells (human and murine) in full blood (in vivo)
  • IgE titre and cytokine levels (human and murine) in blood plasma (in vivo)
  • Airway remodelling (upper airways and lung, including goblet cell hyperplasia, infiltration of eosinophils, fibrosis, airway narrowing; ex vivo)
  • BALF (bronchoalveolar lavage fluid) immune cell composition, cytokine levels, IgE titre (ex vivo)

Readout parameter

  • Invasive/non-invasive lung function measurements
  • Flow cytometry
  • ELISA/CBA (cytometric bead array)
  • RT-PCR
  • Western Blot
  • Histology/Cytology (various classical histological stains)
  • Immunohistochemistry (human and murine)

Quality management and validation

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric Expertise
  • Internal quality management

References

  • Scholbach J, Schulz A, Westphal F, Egger D, Wege AK, Patties I, Köberle M, Sack U, Lange F. Comparison of hematopoietic stem cells derived from fresh and cryopreserved whole cord blood in the generation of humanized mice. PLoS One 2012; 7(10):e46772