University of Southern California
Cytomegalovirus induced amelogenesis imperfecta.
Degree: MS, Cranio-Facial Biology, 2012, University of Southern California
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.
Advisors/Committee Members: Melnick, Michael (Committee Chair), Sameshima, Glenn (Committee Member), Jaskoll, Tina T. (Committee Member).
Subjects/Keywords: cytomegalovirus; cmv; tooth; amelogenesis imperfecta
to Zotero / EndNote / Reference
APA (6th Edition):
Abichaker, G. (2012). Cytomegalovirus induced amelogenesis imperfecta. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30882/rec/1750
Chicago Manual of Style (16th Edition):
Abichaker, George. “Cytomegalovirus induced amelogenesis imperfecta.” 2012. Masters Thesis, University of Southern California. Accessed November 13, 2019.
MLA Handbook (7th Edition):
Abichaker, George. “Cytomegalovirus induced amelogenesis imperfecta.” 2012. Web. 13 Nov 2019.
Abichaker G. Cytomegalovirus induced amelogenesis imperfecta. [Internet] [Masters thesis]. University of Southern California; 2012. [cited 2019 Nov 13].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30882/rec/1750.
Council of Science Editors:
Abichaker G. Cytomegalovirus induced amelogenesis imperfecta. [Masters Thesis]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30882/rec/1750