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Degree

PhD, University of Cincinnati, Medicine : Cell & Molecular Biology, 2002.

Abstract

The goal of my thesis was to gain an understanding of how the Type III intermediate filament (IF) gene peripherin is expressed in a cell type-specific manner and activated in response to nerve injury. The peripherin gene is expressed almost exclusively in neurons of the peripheral nervous system (PNS) that have the ability to regenerate. Previous studies suggested that both 5' flanking sequence and intragenic regions were required for cell type-specific and injury-specific expression (Belecky-Adams et al ., 1993). My worked focused how the intragenic regions of the peripherin gene are controlling gene expression. To determine the intragenic regions that are critical for regulating peripherin gene expression, transgenic mice were generated that expressed peripherin transgenes lacking different introns. Analyses of these mice revealed that deletion of introns 2 through 8 had no effect on either the cell type-specific or injury-specific expression of the peripherin gene. Further, a transgene lacking intron 1 did not display accurate cell type-specific expression, but was activated after injury. Thus, accurate cell type-specific peripherin gene expression depends on elements within intron 1, but other sequences, most likely in the 5'flanking region, are required for activating the peripherin gene in response to nerve injury. Activation of the peripherin gene after nerve injury suggests that the peripherin proteins may have critical functions during nerve re-growth. Studies to determine the function of the peripherin IF network in the formation of neurite in vitro showed that an intact peripherin network is essential for maintenance/formation of long-branch neurite trees and for normal mitochondrial distribution.

Keywords

periphen; gene registration; nerve injury

Advisor

Dr. Linda M. Parysek

Pages

135p.

Document number: ucin1029167857
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1029167857

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