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

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.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2014

Author dc:creator

• McLaughlin, Brandon Kyle

Advisor dc:contributor.advisor

• Balciuniene, Jorune

Committee member dc:contributor.committeemember

• Gruberg, Edward R.

• Biology
• Atp1a3a
• Molecular Genetics
• Nervous System
• Zebrafish

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Dc Identifier Other

904556356

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/3267