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VARIATION IN GALR1 EXPRESSION DETERMINES THE SUSCEPTIBILITY
TO EXCITOTOXIN-INDUCED NEURONAL DEATH IN MICE
by
Seogkyoung Kong
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
May 2007
Copyright 2007 Seogkyoung Kong
Object Description
| Title | Variation in Galr1 expression determines the susceptibility to excitotoxin-induced neuronal death in mice |
| Author | Kong, Seogkyoung |
| Author email | seogkyok@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2007-01-17 |
| Date submitted | 2007 |
| Restricted until | Restricted until 25 March 2009. |
| Date published | 2009-03-25 |
| Advisor (committee chair) | Stallcup, Michael R. |
| Advisor (committee member) |
Schauwecker, P. Elyse [illegible] [illegible] |
| Abstract | Glutamate excitotoxicity plays a role in neuronal death in diverse neurodegenerative diseases. Inbred strains of mice differ in their susceptibility to excitotoxin-induced cell death, but the genetic basis of individual variation in the differential susceptibility is unknown. We localized the genetic loci that contribute to the differential susceptibility to kainic acid (KA)-induced excitotoxic cell death between C57BL/6J and FVB/NJ strains. We confirmed that distal chromosome 18 contains a gene(s) conferring the differential susceptibility through the generation of congenic strains. We identified two potential candidates, Galr1 and Mbp, based on their putative role in modulating excitatory amino acid-related cell death. We used an integrative approach of gene expression in the congenic strain, sequence analysis, and association study with inbred strains of mice that segregate for the trait of susceptibility to KA-induced excitotoxic cell death to determine whether Galr1 and/or Mbp is a causal susceptibility gene(s). Integrative approach of genetic mapping, gene expression traits, sequence analysis, and association study was effective for identifying Galr1 as a putative causal susceptibility gene influencing the differential susceptibility to KA-induced excitotoxic cell death in mice. Our finding will provide novel insights into the molecular determinants critical for excitotoxic cell death in humans as well as in mice. |
| Keyword | glutamate excitotoxicity; genetic variation; Galr1; inbred and congenic mouse models |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m320 |
| Rights | Kong, Seogkyoung |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Kong-20070325 |
| Archival file | uscthesesreloadpub_Volume51/etd-Kong-20070325.pdf |
Description
| Title | Page 1 |
| Full text | VARIATION IN GALR1 EXPRESSION DETERMINES THE SUSCEPTIBILITY TO EXCITOTOXIN-INDUCED NEURONAL DEATH IN MICE by Seogkyoung Kong A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOCHEMISTRY AND MOLECULAR BIOLOGY) May 2007 Copyright 2007 Seogkyoung Kong |
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