Characterization o f Zebrafish Mutant m erlot as a Non-Mammalian Vertebrate Model for Congenital Anemia Due to Protein 4.1 Deficiency

Hdl Handle:
http://hdl.handle.net/10675.2/575212
Title:
Characterization o f Zebrafish Mutant m erlot as a Non-Mammalian Vertebrate Model for Congenital Anemia Due to Protein 4.1 Deficiency
Authors:
Shafizadeh, Ebrahim
Abstract:
The zebrafish mutant merlot (mot) is characterized by onset o f a severe anemia at 96 hours post fertilization. We performed whole mount RNA in situ hybridization and showed that the process o f primitive erythropoiesis is not interrupted in the mot embryos. Blood analysis demonstrated that mot suffers from a severe congenital hemolytic anemia. Using the TU N E L assay, we detected apoptotic erythroid progenitors in the kidneys. We performed electron microscopic analysis and detected membrane abnormalities and a loss o f the cortical membrane organization in the mot cells. We used positional cloning techniques w ith a candidate gene approach to demonstrate that mot encodes the erythroid specific isoform o f protein 4.1R, a critical component o f the red blood cell membrane skeleton. Sequence analysis o f 4.IR cD N A detected nonsense point mutations in both alleles o f mot resulting in premature stop codons. We performed linkage analysis and transgenic rescue experiments to provide further confirmation that the molecular defect in the protein 4 .1R is the underlying cause o f anemic phenotype in mot fish. This study presents the zebrafish mutant merlot as the first characterized non-mammalian vertebrate model o f congenital anemia due to a defect in protein 4.1R integrity.
Affiliation:
Not Listed
Issue Date:
Aug-2002
URI:
http://hdl.handle.net/10675.2/575212
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/251496021?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorShafizadeh, Ebrahimen
dc.date.accessioned2015-08-19T02:53:09Zen
dc.date.available2015-08-19T02:53:09Zen
dc.date.issued2002-08en
dc.identifier.urihttp://hdl.handle.net/10675.2/575212en
dc.description.abstractThe zebrafish mutant merlot (mot) is characterized by onset o f a severe anemia at 96 hours post fertilization. We performed whole mount RNA in situ hybridization and showed that the process o f primitive erythropoiesis is not interrupted in the mot embryos. Blood analysis demonstrated that mot suffers from a severe congenital hemolytic anemia. Using the TU N E L assay, we detected apoptotic erythroid progenitors in the kidneys. We performed electron microscopic analysis and detected membrane abnormalities and a loss o f the cortical membrane organization in the mot cells. We used positional cloning techniques w ith a candidate gene approach to demonstrate that mot encodes the erythroid specific isoform o f protein 4.1R, a critical component o f the red blood cell membrane skeleton. Sequence analysis o f 4.IR cD N A detected nonsense point mutations in both alleles o f mot resulting in premature stop codons. We performed linkage analysis and transgenic rescue experiments to provide further confirmation that the molecular defect in the protein 4 .1R is the underlying cause o f anemic phenotype in mot fish. This study presents the zebrafish mutant merlot as the first characterized non-mammalian vertebrate model o f congenital anemia due to a defect in protein 4.1R integrity.en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/251496021?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectZebrafishen
dc.subjectCongenital anemiaen
dc.subjectHereditary elliptocytosisen
dc.subjectProtein 4.1en
dc.subjectHematopoiesisen
dc.subjectIneffective erythropoiesisen
dc.subjectLinkage analysisen
dc.titleCharacterization o f Zebrafish Mutant m erlot as a Non-Mammalian Vertebrate Model for Congenital Anemia Due to Protein 4.1 Deficiencyen
dc.typeDissertationen
dc.contributor.departmentNot Listeden
dc.description.advisorLin, Shuoen
dc.description.committeeMunn, David; Condie, Brian; Iwashima, Makio; Anderson, Marken
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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