Dysregulation of Circadian Rhythm Gene Expression in Cystic Fibrosis Mice
Autor: | Paul Litman, Eric Barbato, Hannah Mianzo, Rebecca J. Darrah |
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Rok vydání: | 2019 |
Předmět: |
circadian rhythm
medicine.medical_specialty Cystic Fibrosis Physiology Circadian clock gene expression 030209 endocrinology & metabolism Cystic fibrosis 03 medical and health sciences 0302 clinical medicine Internal medicine Gene expression medicine Circadian rhythm lcsh:QH301-705.5 biology Endocrine and Autonomic Systems business.industry Sleep apnea medicine.disease Sleep in non-human animals Cystic fibrosis transmembrane conductance regulator Endocrinology Real-time polymerase chain reaction lcsh:Biology (General) biology.protein business 030217 neurology & neurosurgery Research Article |
Zdroj: | Journal of Circadian Rhythms Journal of Circadian Rhythms, Vol 17, Iss 1 (2019) Journal of Circadian Rhythms; Vol 17 (2019); 2 |
ISSN: | 1740-3391 |
Popis: | Cystic fibrosis (CF) is autosomal recessive disease that affects multiple body systems. CF patients often experience sleep disturbances, altered sleep patterns, and sleep apnea. Sleep in mammals is controlled in part by circadian clock genes, including 'Clock, Bmal1, Period1, Period2, Cryptochrome1,' and 'Cryptochrome2'. The purpose of this study was to gain a better understanding of the biological underpinnings of disordered sleep experienced in CF. To accomplish this, we evaluated circadian clock gene expression profiles in CF and wildtype mice, divided into two subgroups each based on sleep condition. One subgroup of each genotype was permitted to maintain their sleep-wake cycle while the other was deprived of sleep for six hours prior to sacrifice. Brain, skeletal muscle, jejunum, colon, lung and adipose tissues were collected from each mouse. Quantitative polymerase chain reaction (PCR) was used to quantify expression of 'Clock, Bmal1, Period1, Period2, Cryptochrome1' and 'Cryptochrome2', and expression levels were compared between study groups. Our comparisons showed distinct differences between the CF groups and the wildtype groups under both sleep conditions. Additionally, we found the CF mice that had been sleep deprived had severely dysregulated expression of all measured genes in the lung apart from 'Cry1'. Our findings suggest that (1) disordered sleep in CF may be caused by circadian system dysregulation and (2) the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) is a causative factor in the dysregulated circadian clock gene expression profiles of CF mice. |
Databáze: | OpenAIRE |
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