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Characterization of voltage-gated so...
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Linares, Alicia Esther.
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Characterization of voltage-gated sodium channel genes expressed in zebrafish embryos.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Characterization of voltage-gated sodium channel genes expressed in zebrafish embryos./
作者:
Linares, Alicia Esther.
面頁冊數:
242 p.
附註:
Adviser: Angeles Ribera.
Contained By:
Dissertation Abstracts International63-11B.
標題:
Biology, Animal Physiology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3069588
ISBN:
0493892966
Characterization of voltage-gated sodium channel genes expressed in zebrafish embryos.
Linares, Alicia Esther.
Characterization of voltage-gated sodium channel genes expressed in zebrafish embryos.
- 242 p.
Adviser: Angeles Ribera.
Thesis (Ph.D.)--University of Colorado Health Sciences Center, 2002.
Assignment of specific functions to the large number of ion channels is a difficult task. Some light has been shed on this problem with the discovery of human ion channelopathies. However, the symptoms of most channelopathies are present only in the adult. Thus, these conditions offer little insight into the roles ion channels might play during embryonic development. Large-scale mutagenesis screens in zebrafish have provided phenotypic candidates for mutated ion channel genes in the embryo. One of these mutants, macho (<italic>mao </italic>), has an altered touch response (at 27 hpf) and reduction in sodium current amplitude in mechanosensory spinal cord neurons (R-B cells) and retinal ganglion cells. These data suggest that <italic>mao</italic> is a gene required for formation of functional sodium channels. Thus, I hypothesized that <italic> mao</italic> codes for a structural alpha or Na<sub>V</sub>1 gene expressed in R-B cells during embryonic development.
ISBN: 0493892966Subjects--Topical Terms:
1017835
Biology, Animal Physiology.
Characterization of voltage-gated sodium channel genes expressed in zebrafish embryos.
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Assignment of specific functions to the large number of ion channels is a difficult task. Some light has been shed on this problem with the discovery of human ion channelopathies. However, the symptoms of most channelopathies are present only in the adult. Thus, these conditions offer little insight into the roles ion channels might play during embryonic development. Large-scale mutagenesis screens in zebrafish have provided phenotypic candidates for mutated ion channel genes in the embryo. One of these mutants, macho (<italic>mao </italic>), has an altered touch response (at 27 hpf) and reduction in sodium current amplitude in mechanosensory spinal cord neurons (R-B cells) and retinal ganglion cells. These data suggest that <italic>mao</italic> is a gene required for formation of functional sodium channels. Thus, I hypothesized that <italic> mao</italic> codes for a structural alpha or Na<sub>V</sub>1 gene expressed in R-B cells during embryonic development.
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Five zebrafish Na<sub>V</sub>1 cDNA clones were isolated in this study to provide candidates for <italic>mao</italic>. Based on amino acid identity with mammalian Na<sub>V</sub>1 subunits and <italic>in situ</italic> hybridization patterns, orthologues of Na<sub>V</sub>1.2, Na<sub>V</sub>1.4, Na<sub>V</sub>1.5, Na<sub>V</sub>1.6 and Na<sub>V</sub>1.7 were assigned to the isolated zebrafish cDNAs. Further, Na<sub>V</sub>1.6 and Na<sub>V</sub>1.7 were the best candidates for <italic>mao</italic> based on their mRNA expression patterns in the R-B cells.
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Using gene mapping, the genomic locations of zNa<sub>V</sub>1.6 and zNa<sub> V</sub>1.7 were compared to that of the <italic>mao</italic> mutation. These data indicate that neither zNa<sub>V</sub>1.6 nor zNa<sub>V</sub>1.7 is the gene that harbors the <italic>mao</italic> mutation. In addition, the mapping and molecular data gleaned from the zNa<sub>V</sub>1 genes provides a unique look at how Na<sub>V</sub>1 genes may have evolved in the zebrafish. Two new hypotheses were also tested about where the <italic>mao</italic> mutation may lie in the formation of a sodium channel complex containing zNa<sub>V </sub>1.6 and/or zNa<sub>V</sub>1.7 channels in R-B cells.
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In sum, many good candidates for <italic>mao</italic> have been ruled out in these studies. With the completion of the zebrafish genome on the horizon (2003), the role of many new genes that function in the sodium channel pathway will be elucidated, revealing new genes involved in ion channel function as well as the identity of <italic>mao</italic>.
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