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    Disruption of gene expression rhythms in mice lacking secretory vesicle proteins IA-2 and IA-2β

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    Authors
    Punia, Sohan
    Rumery, Kyle K.
    Yu, Elizabeth A.
    Lambert, Christopher M.
    Notkins, Abner L.
    Weaver, David R.
    Student Authors
    Elizabeth Yu
    Kyle R. Rumery
    Academic Program
    MD/PhD
    UMass Chan Affiliations
    Graduate School of Biomedical Sciences, MD/PhD Program
    Weaver Lab
    Neurobiology
    Document Type
    Journal Article
    Publication Date
    2012-09-15
    Keywords
    Animals
    Circadian Rhythm
    Crosses, Genetic
    Dexamethasone
    Female
    Gene Expression Regulation
    Glucocorticoids
    Heart
    Liver
    Male
    Membrane Proteins
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Myocardium
    Neurons
    Organ Specificity
    Protein Isoforms
    RNA, Messenger
    Receptor-Like Protein Tyrosine Phosphatases, Class 8
    Secretory Vesicles
    Suprachiasmatic Nucleus
    UMCCTS funding
    Cellular and Molecular Physiology
    Neuroscience and Neurobiology
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468428/
    Abstract
    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.
    Source
    Am J Physiol Endocrinol Metab. 2012 Sep 15;303(6):E762-76. doi: 10.1152/ajpendo.00513.2011. Epub 2012 Jul 11. Link to article on publisher's website
    DOI
    10.1152/ajpendo.00513.2011
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33268
    PubMed ID
    22785238
    Notes

    Kyle Rumery participated in this study as part of the University of Massachusetts Medical School Summer Undergraduate Research Program.

    Related Resources

    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1152/ajpendo.00513.2011
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    Collections
    Morningside GSBS Scholarly Publications
    Neurobiology Student Publications
    Neurobiology Faculty Publications
    UMass Center for Clinical and Translational Science Supported Publications

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