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CYTOMEGALOVIRUS INDUCED AMELOGENESIS IMPERFECTA
by
George Abichaker
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CRANIOFACIAL BIOLOGY)
May 2012
Copyright 2012 George Abichaker
Object Description
| Title | Cytomegalovirus induced amelogenesis imperfecta |
| Author | Abichaker, George |
| Author email | abichake@usc.edu;georgeabichaker.usc@gamil.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2012-02-21 |
| Date submitted | 2012-05-04 |
| Date approved | 2012-05-04 |
| Restricted until | 2012-05-04 |
| Date published | 2012-05-04 |
| Advisor (committee chair) | Melnick, Michael |
| Advisor (committee member) |
Sameshima, Glenn Jaskoll, Tina T. |
| Abstract | BACKGROUND: Cytomegalovirus (CMV) is one of the most common causes of major birth defects in humans. Of the approximately 8400 children born each year in the U.S. with CMV-induced birth defects, more than 1/3 of these children exhibit hypoplasia and hypocalcification of tooth enamel. ❧ OBJECTIVE: Our objective was to initiate the investigation of the pathogenesis of CMV-induced tooth defects and examine the effects of CMV infection on progressive tooth differentiation and amelogenesis. ❧ METHODS: Mouse Cap and Bell stage mandibular first molars were infected with mouse CMV (mCMV) in vitro in a chemically-defined organ culture system and analyzed utilizing histological and immunolocalization methodologies. ❧ RESULTS: CMV infection of embryonic mouse mandibular first molars in vitro induces tooth dysmorphogenesis and enamel defects in a developmental stage- and duration-dependent manner. Initial protein localization studies suggest that the pathogenesis is mediated through NF-κB signaling and that there appears to be an unusual interaction between abnormal mesenchymal cells and surrounding matrix. Rescue with acyclovir indicates that mCMV replication is necessary to initiate and sustain progressive tooth dysmorphogenesis. Cap stage- and Early Bell stage-infected molars exhibit enamel agenesis and Bell stage-infected molars exhibit enamel hypoplasia. ❧ CONCLUSIONS: Our results indicate that mCMV-induced changes in signaling pathways severely delays, but does not completely interrupt, tooth morphogenesis. This viral-induced pathology is coincident with stage-dependent changes in Amelx, Enam and Dspp gene expression, distribution of amelogenin, enamelin, C/EBPα and DSP proteins, cell proliferation localization and dedifferentiation of secretory ameloblasts. Our data indicate that specific levels of Amelx and Dspp gene expression define whether mouse CMV induces enamel agenesis or hypoplasia. Importantly, our results demonstrate that this well-defined embryonic mouse organ culture system can be utilized to delineate the molecular mechanism underlying the CMV-induced tooth defects that characterize the amelogenesis imperfecta phenocopy seen in many CMV-infected children. |
| Keyword | cytomegalovirus; cmv; tooth; amelogenesis imperfecta |
| 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 |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Abichaker, George |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@dots.usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-AbichakerG-771.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | CYTOMEGALOVIRUS INDUCED AMELOGENESIS IMPERFECTA by George Abichaker A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (CRANIOFACIAL BIOLOGY) May 2012 Copyright 2012 George Abichaker |
