Gene Changes in Mice Without Tryptophan Hydroxylase-1 and Their Implications for Lung Disease
Author Information
Author(s): Rothman Richard B., Cadet Jean L., Dersch Christina M., McCoy Michael T., Lehrmann Elin, Becker Kevin G., Bader Michael, Alenina Natalia, Baumann Michael H.
Primary Institution: National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States of America
Hypothesis
Tph1(−/−) mice express lower levels of pulmonary 5-HT transporter (SERT) compared to wild-type controls and display adaptive changes in the expression of non-serotonergic pulmonary genes implicated in pulmonary arterial hypertension (PAH).
Conclusion
The study found that female Tph1(−/−) mice are protected from dexfenfluramine-induced pulmonary arterial hypertension due to compensatory changes in gene expression.
Supporting Evidence
- The number of pulmonary SERT sites was modestly up-regulated in female Tph1(−/−) mice.
- 51 distinct genes were significantly altered in the lungs of female Tph1(−/−) mice.
- Three genes implicated in PAH were markedly up-regulated in Tph1(−/−) mice.
Takeaway
Researchers studied mice that lack a specific gene and found that these mice are less likely to develop a lung disease caused by a certain drug, possibly because their bodies adapt in other ways.
Methodology
The study used radioligand binding methods to measure SERT and microarrays followed by quantitative real-time PCR to analyze gene expression.
Limitations
The study cannot determine which specific tissue type exhibits the changes in gene expression noted, as whole lungs were used in the experiments.
Participant Demographics
Female Tph1(−/−) and wild-type mice were used in the experiments.
Statistical Information
P-Value
p<0.025
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website