{"id":{"repo_id":"texas","oai_identifier":"oai:repositories.lib.utexas.edu:2152/89285"},"canonical_url":"https://search.dev.ndltd.org/etd/texas/oai:repositories.lib.utexas.edu:2152/89285","repository":{"repo_id":"texas","name":"University of Texas","base_url":"https://repositories.lib.utexas.edu/server/oai/request"},"display":{"title":"A novel low-density lipoprotein receptor-related protein protects against environmental teratogens","abstract":"Congenital malformations are the leading cause of infant mortality in the United States, and 2% of all live births have some form of malformation. While many of these malformations have known genetic or environmental causes, others have eluded explanation. These conditions are thought to be caused by complex interaction between genetic and environmental factors. Prenatal ethanol exposure results in the highest number of preventable birth defects in the United States. Prenatal ethanol exposure interacts with another well-established teratogen: prenatal hyperthermia. Additionally, each of these teratogens interacts with the genetics of the exposed individual. A foreword genetic screen identified a mutation in an uncharacterized locus that sensitizes developing zebrafish to both prenatal ethanol exposure and increased developmental temperature. I identified this locus as a member of the low-density lipoprotein receptor-related protein (LRP) family, and designated it lrp13b. I have found that ethanol teratogenesis in lrp13b mutants is made more severe by increased developmental temperature. Mutants in lrp13b experienced increased apoptosis and fail to properly differentiate facial cartilages when exposed to environmental teratogens. My data suggest that the protective role of lrp13b during development is due to interaction with the fibroblast growth factor (FGF) signaling pathway in the post migratory cranial neural crest. Collectively, these data characterize a novel genetic locus and provide insight into the complex multifactorial etiology of congenital malformations.","abstract_html":"Congenital malformations are the leading cause of infant mortality in the United States, and 2% of all live births have some form of malformation. While many of these malformations have known genetic or environmental causes, others have eluded explanation. These conditions are thought to be caused by complex interaction between genetic and environmental factors. Prenatal ethanol exposure results in the highest number of preventable birth defects in the United States. Prenatal ethanol exposure interacts with another well-established teratogen: prenatal hyperthermia. Additionally, each of these teratogens interacts with the genetics of the exposed individual. A foreword genetic screen identified a mutation in an uncharacterized locus that sensitizes developing zebrafish to both prenatal ethanol exposure and increased developmental temperature. I identified this locus as a member of the low-density lipoprotein receptor-related protein (LRP) family, and designated it lrp13b. I have found that ethanol teratogenesis in lrp13b mutants is made more severe by increased developmental temperature. Mutants in lrp13b experienced increased apoptosis and fail to properly differentiate facial cartilages when exposed to environmental teratogens. My data suggest that the protective role of lrp13b during development is due to interaction with the fibroblast growth factor (FGF) signaling pathway in the post migratory cranial neural crest. Collectively, these data characterize a novel genetic locus and provide insight into the complex multifactorial etiology of congenital malformations.","abstract_has_math":false,"creators":["Kuka, Timothy Paul"],"institution":"The University of Texas at Austin","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Cell and Molecular Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Eberhart, Johann K."],"committee_chairs":[],"committee_members":["Gonzales, Rueben A","Gray, Ryan S","Pierce, Jonathan T","Vokes, Steven A"],"year":2021,"date_issued":"2021-08-11","date_published":"2021-08-11","updated_at":"2026-07-24T05:01:04Z","subjects":["FASD","LRP","Development","Zebrafish","Neural crest"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152/89285","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Eberhart, Johann K."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Gonzales, Rueben A","Gray, Ryan S","Pierce, Jonathan T","Vokes, Steven A"]},{"key":"dc:creator","label":"Author","values":["Kuka, Timothy Paul"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-10-18T23:06:16Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-10-18T23:06:16Z"]},{"key":"dc:date.issued","label":"Date","values":["2021-08-11"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Molecular Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas at Austin"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["FASD","LRP","Development","Zebrafish","Neural crest"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152/89285"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Congenital malformations are the leading cause of infant mortality in the United States, and 2% of all live births have some form of malformation. While many of these malformations have known genetic or environmental causes, others have eluded explanation. These conditions are thought to be caused by complex interaction between genetic and environmental factors. Prenatal ethanol exposure results in the highest number of preventable birth defects in the United States. Prenatal ethanol exposure interacts with another well-established teratogen: prenatal hyperthermia. Additionally, each of these teratogens interacts with the genetics of the exposed individual. A foreword genetic screen identified a mutation in an uncharacterized locus that sensitizes developing zebrafish to both prenatal ethanol exposure and increased developmental temperature. I identified this locus as a member of the low-density lipoprotein receptor-related protein (LRP) family, and designated it lrp13b. I have found that ethanol teratogenesis in lrp13b mutants is made more severe by increased developmental temperature. Mutants in lrp13b experienced increased apoptosis and fail to properly differentiate facial cartilages when exposed to environmental teratogens. My data suggest that the protective role of lrp13b during development is due to interaction with the fibroblast growth factor (FGF) signaling pathway in the post migratory cranial neural crest. Collectively, these data characterize a novel genetic locus and provide insight into the complex multifactorial etiology of congenital malformations."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["A novel low-density lipoprotein receptor-related protein protects against environmental teratogens"]}]}],"canonical_facts":{"dc:contributor.advisor":["Eberhart, Johann K."],"dc:contributor.committeemember":["Gonzales, Rueben A","Gray, Ryan S","Pierce, Jonathan T","Vokes, Steven A"],"dc:creator":["Kuka, Timothy Paul"],"dc:date.accessioned":["2021-10-18T23:06:16Z"],"dc:date.available":["2021-10-18T23:06:16Z"],"dc:date.issued":["2021-08-11"],"dc:description.abstract":["Congenital malformations are the leading cause of infant mortality in the United States, and 2% of all live births have some form of malformation. While many of these malformations have known genetic or environmental causes, others have eluded explanation. These conditions are thought to be caused by complex interaction between genetic and environmental factors. Prenatal ethanol exposure results in the highest number of preventable birth defects in the United States. Prenatal ethanol exposure interacts with another well-established teratogen: prenatal hyperthermia. Additionally, each of these teratogens interacts with the genetics of the exposed individual. A foreword genetic screen identified a mutation in an uncharacterized locus that sensitizes developing zebrafish to both prenatal ethanol exposure and increased developmental temperature. I identified this locus as a member of the low-density lipoprotein receptor-related protein (LRP) family, and designated it lrp13b. I have found that ethanol teratogenesis in lrp13b mutants is made more severe by increased developmental temperature. Mutants in lrp13b experienced increased apoptosis and fail to properly differentiate facial cartilages when exposed to environmental teratogens. My data suggest that the protective role of lrp13b during development is due to interaction with the fibroblast growth factor (FGF) signaling pathway in the post migratory cranial neural crest. Collectively, these data characterize a novel genetic locus and provide insight into the complex multifactorial etiology of congenital malformations."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2152/89285"],"dc:language.iso":["en"],"dc:subject":["FASD","LRP","Development","Zebrafish","Neural crest"],"dc:title":["A novel low-density lipoprotein receptor-related protein protects against environmental teratogens"],"dc:type":["Thesis"],"thesis:degree_discipline":["Cell and Molecular Biology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["The University of Texas at Austin"]},"updated_at":"2026-07-24T05:01:04Z"}