Plp1 gene duplication inhibits airway responsiveness and induces lung inflammation.
Publication/Presentation Date
2-1-2015
Abstract
Mice with Plp1 gene duplication model the most common form of Pelizaeus-Merzbacher disease (PMD), a CNS disease in which patients may suffer respiratory complications. We hypothesized that affected mice would lack airway responsiveness compared to wild-type and carrier mice during methacholine challenge. Wild-type (n = 10), carrier female (n = 6) and affected male (n = 8) mice were anesthetized-paralyzed, tracheostomized and ventilated. Respiratory mechanics were recorded at baseline and during escalating doses of nebulized methacholine followed by albuterol. Lung resistance (RL) was the primary endpoint. Lung tissues were assayed for inflammatory and histological differences. At baseline, phase angles were higher in carrier and affected mice than wild-type. Dose-response RL curves in affected and carrier mice indicated a lack of methacholine response. Albuterol reduced RL in wild-type and carrier, but not affected mice. Affected mice exhibited lower interleukin (IL)-6 tissue levels and alveolar inflammatory infiltrates. Affected and carrier mice, compared to wild-type, lacked airway reactivity during methacholine challenge, but only affected mice exhibited decreased lung tissue levels of IL-6 and inflammation.
Volume
30
First Page
22
Last Page
31
ISSN
1522-9629
Published In/Presented At
Rodriguez, E., Sakowski, L., Hobson, G. M., Armani, M. H., Kreiger, P. A., Zhu, Y., Waldman, S. A., & Shaffer, T. H. (2015). Plp1 gene duplication inhibits airway responsiveness and induces lung inflammation. Pulmonary pharmacology & therapeutics, 30, 22–31. https://doi.org/10.1016/j.pupt.2014.10.004
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
25445931
Department(s)
Administration and Leadership
Document Type
Article