Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease

(1) Background: We sought to investigate the baseline lung and heart biology of the Dp16 mouse model of Down syndrome (DS) as a prelude to the investigation of recurrent respiratory tract infection. (2) Methods: In controls vs. Dp16 mice, we compared peripheral blood cell and plasma analytes. We exa...

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Published in:	Genes 2023-09, Vol.14 (9), p.1819
Main Authors:	Colvin, Kelley L, Nguyen, Kathleen, Boncella, Katie L, Goodman, Desiree M, Elliott, Robert J, Harral, Julie W, Bilodeaux, Jill, Smith, Bradford J, Yeager, Michael E
Format:	Article
Language:	eng
Subjects:	Analysis Animals B cells Bacterial infections Biological response modifiers Biology Bronchopulmonary infection Bronchus bronchus-associated lymphoid tissue Catheters Chemokines Chromosomes Disease Models, Animal Disease susceptibility Down syndrome Down Syndrome - metabolism Down's syndrome Euthanasia Female Gene expression Genes Health aspects Heart Hemodynamics Humans Hypotonicity Infection Influenza Interferon interferons Ketamine Laboratory animals Lung - metabolism Lungs Lymphoid tissue Male Medical research Medicine, Experimental Mice Morphometry Mortality mouse model Peripheral blood Platelet-activating factor Polymerase chain reaction Pulmonary function tests Recurrent infection Respiratory function Respiratory system Respiratory tract infection Respiratory Tract Infections RNA Stat3 protein Streptococcus infections Ventilators α-Interferon
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Summary:	(1) Background: We sought to investigate the baseline lung and heart biology of the Dp16 mouse model of Down syndrome (DS) as a prelude to the investigation of recurrent respiratory tract infection. (2) Methods: In controls vs. Dp16 mice, we compared peripheral blood cell and plasma analytes. We examined baseline gene expression in lungs and hearts for key parameters related to susceptibility of lung infection. We investigated lung and heart protein expression and performed lung morphometry. Finally, and for the first time each in a model of DS, we performed pulmonary function testing and a hemodynamic assessment of cardiac function. (3) Results: Dp16 mice circulate unique blood plasma cytokines and chemokines. Dp16 mouse lungs over-express the mRNA of triplicated genes, but not necessarily corresponding proteins. We found a sex-specific decrease in the protein expression of interferon α receptors, yet an increased signal transducer and activator of transcription (STAT)-3 and phospho-STAT3. Platelet-activating factor receptor protein was not elevated in Dp16 mice. The lungs of Dp16 mice showed increased stiffness and mean linear intercept and contained bronchus-associated lymphoid tissue. The heart ventricles of Dp16 mice displayed hypotonicity. Finally, Dp16 mice required more ketamine to achieve an anesthetized state. (4) Conclusions: The Dp16 mouse model of DS displays key aspects of lung heart biology akin to people with DS. As such, it has the potential to be an extremely valuable model of recurrent severe respiratory tract infection in DS.
ISSN:	2073-4425 2073-4425