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dc.contributor.authorPunia, Sohan
dc.contributor.authorRumery, Kyle K.
dc.contributor.authorYu, Elizabeth A.
dc.contributor.authorLambert, Christopher M.
dc.contributor.authorNotkins, Abner L.
dc.contributor.authorWeaver, David R.
dc.date2022-08-11T08:08:54.000
dc.date.accessioned2022-08-23T16:11:51Z
dc.date.available2022-08-23T16:11:51Z
dc.date.issued2012-09-15
dc.date.submitted2012-12-19
dc.identifier.citationAm J Physiol Endocrinol Metab. 2012 Sep 15;303(6):E762-76. doi: 10.1152/ajpendo.00513.2011. Epub 2012 Jul 11. <a href="http://dx.doi.org/10.1152/ajpendo.00513.2011">Link to article on publisher's website</a>
dc.identifier.issn1522-1555
dc.identifier.doi10.1152/ajpendo.00513.2011
dc.identifier.pmid22785238
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33268
dc.description<p>Kyle Rumery participated in this study as part of the University of Massachusetts Medical School Summer Undergraduate Research Program.</p>
dc.description.abstractInsulinoma-associated protein (IA)-2 and IA-2β are transmembrane proteins involved in neurotransmitter secretion. Mice with targeted disruption of both IA-2 and IA-2β (double-knockout, or DKO mice) have numerous endocrine and physiological disruptions, including disruption of circadian and diurnal rhythms. In the present study, we have assessed the impact of disruption of IA-2 and IA-2β on molecular rhythms in the brain and peripheral oscillators. We used in situ hybridization to assess molecular rhythms in the hypothalamic suprachiasmatic nuclei (SCN) of wild-type (WT) and DKO mice. The results indicate significant disruption of molecular rhythmicity in the SCN, which serves as the central pacemaker regulating circadian behavior. We also used quantitative PCR to assess gene expression rhythms in peripheral tissues of DKO, single-knockout, and WT mice. The results indicate significant attenuation of gene expression rhythms in several peripheral tissues of DKO mice but not in either single knockout. To distinguish whether this reduction in rhythmicity reflects defective oscillatory function in peripheral tissues or lack of entrainment of peripheral tissues, animals were injected with dexamethasone daily for 15 days, and then molecular rhythms were assessed throughout the day after discontinuation of injections. Dexamethasone injections improved gene expression rhythms in liver and heart of DKO mice. These results are consistent with the hypothesis that peripheral tissues of DKO mice have a functioning circadian clockwork, but rhythmicity is greatly reduced in the absence of robust, rhythmic physiological signals originating from the SCN. Thus, IA-2 and IA-2β play an important role in the regulation of circadian rhythms, likely through their participation in neurochemical communication among SCN neurons.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22785238&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468428/
dc.subjectAnimals
dc.subjectCircadian Rhythm
dc.subjectCrosses, Genetic
dc.subjectDexamethasone
dc.subjectFemale
dc.subjectGene Expression Regulation
dc.subjectGlucocorticoids
dc.subjectHeart
dc.subjectLiver
dc.subjectMale
dc.subjectMembrane Proteins
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMyocardium
dc.subjectNeurons
dc.subjectOrgan Specificity
dc.subjectProtein Isoforms
dc.subjectRNA, Messenger
dc.subjectReceptor-Like Protein Tyrosine Phosphatases, Class 8
dc.subjectSecretory Vesicles
dc.subjectSuprachiasmatic Nucleus
dc.subjectUMCCTS funding
dc.subjectCellular and Molecular Physiology
dc.subjectNeuroscience and Neurobiology
dc.titleDisruption of gene expression rhythms in mice lacking secretory vesicle proteins IA-2 and IA-2β
dc.typeJournal Article
dc.source.journaltitleAmerican journal of physiology. Endocrinology and metabolism
dc.source.volume303
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1800
dc.identifier.contextkey3550466
html.description.abstract<p>Insulinoma-associated protein (IA)-2 and IA-2β are transmembrane proteins involved in neurotransmitter secretion. Mice with targeted disruption of both IA-2 and IA-2β (double-knockout, or DKO mice) have numerous endocrine and physiological disruptions, including disruption of circadian and diurnal rhythms. In the present study, we have assessed the impact of disruption of IA-2 and IA-2β on molecular rhythms in the brain and peripheral oscillators. We used in situ hybridization to assess molecular rhythms in the hypothalamic suprachiasmatic nuclei (SCN) of wild-type (WT) and DKO mice. The results indicate significant disruption of molecular rhythmicity in the SCN, which serves as the central pacemaker regulating circadian behavior. We also used quantitative PCR to assess gene expression rhythms in peripheral tissues of DKO, single-knockout, and WT mice. The results indicate significant attenuation of gene expression rhythms in several peripheral tissues of DKO mice but not in either single knockout. To distinguish whether this reduction in rhythmicity reflects defective oscillatory function in peripheral tissues or lack of entrainment of peripheral tissues, animals were injected with dexamethasone daily for 15 days, and then molecular rhythms were assessed throughout the day after discontinuation of injections. Dexamethasone injections improved gene expression rhythms in liver and heart of DKO mice. These results are consistent with the hypothesis that peripheral tissues of DKO mice have a functioning circadian clockwork, but rhythmicity is greatly reduced in the absence of robust, rhythmic physiological signals originating from the SCN. Thus, IA-2 and IA-2β play an important role in the regulation of circadian rhythms, likely through their participation in neurochemical communication among SCN neurons.</p>
dc.identifier.submissionpathgsbs_sp/1800
dc.contributor.departmentGraduate School of Biomedical Sciences, MD/PhD Program
dc.contributor.departmentWeaver Lab
dc.contributor.departmentNeurobiology
dc.source.pagesE762-76
dc.contributor.studentElizabeth Yu
dc.contributor.studentKyle R. Rumery
dc.description.thesisprogramMD/PhD


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