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dc.contributor.advisorRibera, Angeles B.
dc.contributor.authorCarmean, Vanessa
dc.date.accessioned2015-08-27T03:56:13Z
dc.date.available2016-02-19T08:20:26Z
dc.date.submitted2015
dc.identifierCarmean_ucdenveramc_1639D_10252.pdf
dc.identifier.urihttp://hdl.handle.net/10968/1150
dc.descriptionSummer
dc.descriptionIncludes bibliographical references.
dc.description.abstractThe study of touch-evoked behavior allows investigation into the cells, circuits, and specific proteins and channels required for a tactile response. I investigated a mutant zebrafish strain, macho, lacking a touch response and with decreased sodium current amplitudes in sensory neurons. Mutant macho embryos carry a mutation in the pigk gene that is not present in wild type siblings. The pigk gene encodes the protein PigK that is critical for transfer of glycophosphatidylinositol anchors to precursor proteins. It is not understood how a mutation in pigk results in a decrease in sensory neuron sodium current amplitudes or touch response. I provided evidence that pigk is present at the right time to affect the touch response. My data suggests that maternal expression of pigk is a potential explanation for survival of macho mutants to larval stages. I next provided support for the identification of pigk as the gene underlying the macho phenotype through rescue with wild type pigk. I found that the touch response in macho mutants is rescued with ubiquitously expressed wild type pigk. I then expressed wild type pigk specifically in sensory neurons of macho mutants. I used electrophysiology to demonstrate that specific expression of wild type pigk resulted in rescue of voltage-gated sodium current amplitude and the ability to elicit action potentials. However, I found that expression of wild type pigk in these sensory neurons did not rescue the touch response. My work indicates the importance of pigk in the touch circuit, and reveals the need for pigk for more than normal function of INa and action potential firing in RB cells. I discuss potential future directions and implications for the study of the macho mutant and other mutants with decreased touch response.
dc.format.extent96 pages
dc.languageEnglish
dc.language.isoeng
dc.publisherUniversity of Colorado at Denver, Anschutz Medical Campus. Health Sciences Library
dc.rightsCopyright of the original work is retained by the author.
dc.subjectRohon-Beard
dc.subjectGPI-AP
dc.subjectPigK
dc.subject.meshVoltage-Gated Sodium Channels
dc.subject.meshZebrafish
dc.subject.meshNeurosciences
dc.titlePigK underlies macho behavior and is required for Rohon-Beard cell excitability
dc.typeThesis
dc.rights.accessEmbargo Expires: 02/19/2016
dcterms.embargo.terms2016-02-19
dcterms.embargo.expires2016-02-19
dc.contributor.committeememberKinnamon, Sue C.
dc.contributor.committeememberAppel, Bruce
dc.contributor.committeememberCaldwell, John H.
dc.contributor.committeememberTamkun, Michael M.
thesis.degree.nameDoctor of Philosophy (Ph.D.)
thesis.degree.levelDoctoral
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Colorado at Denver, Anschutz Medical Campus


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