Phenotyping and Genetic Studies
Phenotyping and genetic studies of animal models are an important tool for pre-clinical research to learn more about gene function in humans. A single gene can have a different impact and function across multiple organ systems or time points during development. Therefore, the phenotyping process must be highly standardized to enable appearance of certain phenotypes that would otherwise remain hidden. Phenotypes for genetic study must consistently meet high standards of reproducibility and validity.
COMPREHENSIVE AND INTEGRATED ASSESSMENT
Translational research is increasingly important and necessary to better understand disease pathologies. The flexiVent offers precise measurement of lung function in mouse models, which can be used as an initial screen for potential pulmonary phenotypes. These measurements are extremely sensitive and reproducible manoeuvres, which allow small but significant changes to be assessed and offer information about lung structure.
- Application Note: Phenotyping cystic fibrosis with the FX
- Darrah, R. J., et al. (2019). AGTR2 absence or antagonism prevents cystic fibrosis pulmonary manifestations. Journal of Cystic Fibrosis, 18(1), 127-134.
- Fuchs, H., et al. (2018). Understanding gene functions and disease mechanisms: Phenotyping pipelines in the German Mouse Clinic. Behavioural Brain Research, 352, 187-196.
- Borel, F., et al. (2018). Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema. PNAS, 115(11), 2788-2793.
- Reuter, S., et al. (2016). Cylindromatosis (Cyld) gene mutation in T cells promotes the development of an IL-9-dependent allergic phenotype in experimental asthma. Cellular Immunology, 308, 27-34.
COMPACT, REPRODUCIBLE, AUTOMATED
Disease models are often generated by exposing subjects to aerosols, smoke, or vapour using acute or chronic protocols to establish relevant phenotypes. The inExpose has been specifically designed to allow for repetitive precise delivery of the test atmosphere through automated exposure profiles, which also help to reduce user error and minimize outcome variations among subjects, study, and research groups. The inExpose operates under various configurations and protocols to ensure that the subjects receive repeated yet consistent exposure environments throughout experimentation. Generating relevant, practical animal models is key for translating the outcomes from the preclinical environment into a better understanding of disease pathologies
- Wolfson, M. R., Baker, S. T., Tian, Y., Bahmed, K., Kosmider, B., Marcinkiewicz, & Wu, J. (2017). Utility of abbreviated exposure time in mice – Contribution to undersanding pathogenesis of cigarette smoke induced lung disease. The FASEB Journal, 31(1), supplement.
- Raju, S. V., et al. (2016). A ferret model of COPD-related chronic bronchitis, JCI insight, 1(15), e87536.
- Yadav, P., et al. (2017). Genetic factors interact with tobacco smoke to modify risk for inflammatory bowel disease in humans and mice. Gastroenterology, 153(2), 556-565.
- McCormick, L. K., et al. (2018). Maternal smoking induces acquired CFTR dysfunction in neonatal rats. American Journal of Respiratory and Critical Care Medicine, 198(5).
Whole body plethysmography permits a continuous and non-invasive assessment of breathing patterns in conscious subjects. Measurements of respiratory rate, estimated tidal volume, minute ventilation and events like apneas and deep sighs provide valuable insights into the subject’s breathing drive and behavior. Genetic studies using plethysmography techniques evaluate the effects of various genes on breathing control and activity and are often used for screening purposes.
- Peng, X., et al. (2019). Neonatal Streptococus pneumoniae pneumonia induces an aberrant airway smooth muscle phenotype and AHR in mice model. BioMed Research International, 1-8.
- Wu, Y., Zhong, W., Cui, N., Johnson, C. M., Xing, H., Zhang S., & Jiang, C. (2016). Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats. Journal of Neurodevelopmental Disorders, 8(23).
- Vannoy, C. H., Xiao, W., Lu, P., Xiao, X., & Lu, Q. L. (2017). Efficacy of gene therapy is dependent on disease progression in dystrophic mice with mutations in the FKRP gene. Molecular Therapy Methods & Clinical Development, 5, 31-42.
- Ucero, A. C., et al. (2019). Fra-2-expressing macrophages promote lung fibrosis in mice. The Journal of Clinical Investigation.