Significance of Glucose-Regulated Protein GRP170 (ORP150) in Mouse Striatal Development

Hdl Handle:
http://hdl.handle.net/10675.2/325492
Title:
Significance of Glucose-Regulated Protein GRP170 (ORP150) in Mouse Striatal Development
Authors:
Deane, Sadiki
Abstract:
The glucose-regulated protein 170 (Grp170) is a nucleotide exchange factor for Grp78 and they are resident endoplasmic reticulum (ER). Grp170 expresses highly in the brain and removal of Grp170 from the whole body leads to mouse embryonic lethality. Grp170 protein is overexpressed after many cellular stressors and has protective function in neural, renal and cardiac models of ischemia and reperfusion. To understand the function of Grp170 in the brain, we have generated a conditional knockout of Grp170 in mice. We used Nestin Cre recombinase transgenic mice crossed with Grp170Flox/Flox mice to generate Grp170Flox/Flox-Nestin-Cre+ mice, which died upon birth. Therefore we analyzed Grp170Flox/Flox-Nestin-Cre+ embryos between embryonic days E13.5 day to E18.5 day and brain appears normal at this stage. However, at E14.5 to E18.5, there is a significant loss of neuronal cells in the developing striatum and decrease in brain anatomical size and increase in lateral ventricle volume in the absence of Grp170. Thus, we hypothesize that Grp170 Facilitates proper folding and ER transport of oen or more key polypeptide molecule(s) involved in neuronal cell survival in the developing striatum. Interestingly, expression of Grp78 is significantly enhanced in the cortex, striatum and midbrain suggesting the presence of ER stress in cells lacking Grp170 in developing mice.
Issue Date:
Jul-2014
URI:
http://hdl.handle.net/10675.2/325492
Type:
Dissertation
Language:
en
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorDeane, Sadikien
dc.date.accessioned2014-08-27T19:38:57Z-
dc.date.available2014-08-27T19:38:57Z-
dc.date.issued2014-07-
dc.identifier.urihttp://hdl.handle.net/10675.2/325492-
dc.description.abstractThe glucose-regulated protein 170 (Grp170) is a nucleotide exchange factor for Grp78 and they are resident endoplasmic reticulum (ER). Grp170 expresses highly in the brain and removal of Grp170 from the whole body leads to mouse embryonic lethality. Grp170 protein is overexpressed after many cellular stressors and has protective function in neural, renal and cardiac models of ischemia and reperfusion. To understand the function of Grp170 in the brain, we have generated a conditional knockout of Grp170 in mice. We used Nestin Cre recombinase transgenic mice crossed with Grp170Flox/Flox mice to generate Grp170Flox/Flox-Nestin-Cre+ mice, which died upon birth. Therefore we analyzed Grp170Flox/Flox-Nestin-Cre+ embryos between embryonic days E13.5 day to E18.5 day and brain appears normal at this stage. However, at E14.5 to E18.5, there is a significant loss of neuronal cells in the developing striatum and decrease in brain anatomical size and increase in lateral ventricle volume in the absence of Grp170. Thus, we hypothesize that Grp170 Facilitates proper folding and ER transport of oen or more key polypeptide molecule(s) involved in neuronal cell survival in the developing striatum. Interestingly, expression of Grp78 is significantly enhanced in the cortex, striatum and midbrain suggesting the presence of ER stress in cells lacking Grp170 in developing mice.en
dc.language.isoenen
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.-
dc.subjectBrainen
dc.subjectCre Recombinaseen
dc.subjectEmbryoen
dc.subjectEndoplasmic Reticulumen
dc.subjectGrp170en
dc.subjectKnockout Miceen
dc.subjectNestinen
dc.subjectStriatumen
dc.titleSignificance of Glucose-Regulated Protein GRP170 (ORP150) in Mouse Striatal Developmenten
dc.typeDissertationen
dc.description.advisorMivechi, Nahid F.-
dc.description.committeeBeiberich, Erhard; Horuzko, Analojia; Moskophidis, Dimitrios; Xiong, Wencheng; Mivechi, Nahid; Kamitani, Tetsu-
dc.description.degreeMaster of Science (M.S.)-
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