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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/9/1819 |
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| author | Kelley L. Colvin Kathleen Nguyen Katie L. Boncella Desiree M. Goodman Robert J. Elliott Julie W. Harral Jill Bilodeaux Bradford J. Smith Michael E. Yeager |
| author_facet | Kelley L. Colvin Kathleen Nguyen Katie L. Boncella Desiree M. Goodman Robert J. Elliott Julie W. Harral Jill Bilodeaux Bradford J. Smith Michael E. Yeager |
| author_sort | Kelley L. Colvin |
| collection | DOAJ |
| description | (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. |
| first_indexed | 2024-03-10T22:43:49Z |
| format | Article |
| id | doaj.art-e1a13ad713c14e0f8caf7d0086517b75 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T22:43:49Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e1a13ad713c14e0f8caf7d0086517b752023-11-19T10:54:08ZengMDPI AGGenes2073-44252023-09-01149181910.3390/genes14091819Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary DiseaseKelley L. Colvin0Kathleen Nguyen1Katie L. Boncella2Desiree M. Goodman3Robert J. Elliott4Julie W. Harral5Jill Bilodeaux6Bradford J. Smith7Michael E. Yeager8Linda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO 80045, USADepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USALinda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO 80045, USADepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Medicine, University of Colorado, Aurora, CO 80045, USADepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USALinda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO 80045, USA(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.https://www.mdpi.com/2073-4425/14/9/1819respiratory tract infectionDown syndromemouse modelinterferonsbronchus-associated lymphoid tissue |
| spellingShingle | Kelley L. Colvin Kathleen Nguyen Katie L. Boncella Desiree M. Goodman Robert J. Elliott Julie W. Harral Jill Bilodeaux Bradford J. Smith Michael E. Yeager Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease Genes respiratory tract infection Down syndrome mouse model interferons bronchus-associated lymphoid tissue |
| title | Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease |
| title_full | Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease |
| title_fullStr | Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease |
| title_full_unstemmed | Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease |
| title_short | Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease |
| title_sort | lung and heart biology of the dp16 mouse model of down syndrome implications for studying cardiopulmonary disease |
| topic | respiratory tract infection Down syndrome mouse model interferons bronchus-associated lymphoid tissue |
| url | https://www.mdpi.com/2073-4425/14/9/1819 |
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