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    Study of the Functional Role of ATP1A3A in the Vertebrate Nervous System

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    Genre
    Thesis/Dissertation
    Date
    2014
    Author
    McLaughlin, Brandon Kyle
    Advisor
    Balciuniene, Jorune
    Committee member
    Gruberg, Edward R.
    Department
    Biology
    Subject
    Biology
    Atp1a3a
    Molecular Genetics
    Nervous System
    Zebrafish
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/3267
    
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    DOI
    http://dx.doi.org/10.34944/dspace/3249
    Abstract
    Na+, K+ ATPases are a group of transmembrane-bound pumps found in all animal cell types. The primary functions of Na+, K+ ATPases are to maintain electrochemical gradients across cell membranes by actively transporting Na+ and K+ ions between intracellular and extracellular spaces using ATP hydrolysis. In vertebrates, Na+, K+ ATPases come in a variety of different isoforms that are expressed in a variety of tissues. Specifically, the α3 isoform, encoded by gene ATP1A3A in humans, has been shown to be expressed in neurons. Mutations in ATP1A3A have been linked to rapid-onset dystonia-parkinsonism and alternating hemiplegia of childhood in humans and has also been shown to cause motor deficits, neuronal excitability, and perinatal death in various animal models. Our lab has generated a mutant in zebrafish (Danio rerio) containing a gene trap that prematurely stops transcription of the ATP1A3A homolog, atp1a3a. We found that larvae homozygous for the gene trap mutation do not survive past 10 days post fertilization. Further analysis revealed that homozygous mutants show vision deficits. We attempted to rescue these phenotypes by expressing atp1a3a in neurons exclusively. However, no rescue of the larval death or vision abnormality was observed, suggesting that atp1a3a presence in cells other than neurons may be critical for survival and proper visual function of the animal.
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