title: Cytomegalovirus induces stage-dependent enamel defects and misexpression of amelogenin, enamelin and dentin sialophosphoprotein in developing mouse molars.
abstract: Of the approximately 8,400 children born each year in the US with cytomegalovirus (CMV)-induced birth defects, more than one third exhibit hypoplasia and hypocalcification of tooth enamel. Our prior studies indicated that CMV severely delayed, but did not completely interrupt, early mouse mandibular first molar morphogenesis in vitro. The aim of the present study was to examine the effects of CMV infection on progressive tooth differentiation and amelogenesis. Since initial CMV infection in human fetuses can occur at different developmental times, we varied the stage of initial viral infection (that is, Cap stage, Early Bell stage and Bell stage), as well as the duration of infection. CMV infection of embryonic mouse mandibular first molars in vitro induces tooth dysmorphogenesis and enamel defects in a developmental stage- and duration-dependent manner. Cap stage- and Early Bell stage-infected molars exhibit enamel agenesis and Bell stage-infected molars exhibit enamel hypoplasia. This viral-induced pathology is coincident with stage-dependent changes in Amelx, Enam and Dspp gene expression, distribution of amelogenin, enamelin and DSP proteins, cell proliferation localization and dedifferentiation of secretory ameloblasts. Importantly, our data indicate that specific levels of Amelx and Dspp gene expression define whether mouse CMV induces enamel agenesis or hypoplasia.
authors.affiliation: Laboratory for Developmental Genetics, University of Southern California, Los Angeles, CA 90089-0641, USA. tjaskoll@usc.edu
authors.forename: Tina
authors.initials: T
authors.lastname: Jaskoll
authors.forename: George
authors.initials: G
authors.lastname: Abichaker
authors.forename: Khine
authors.initials: K
authors.lastname: Htet
authors.forename: Pablo
authors.initials: P
authors.lastname: Bringas
authors.forename: Scott
authors.initials: S
authors.lastname: Morita
authors.forename: Parish P
authors.initials: PP
authors.lastname: Sedghizadeh
authors.forename: Michael
authors.initials: M
authors.lastname: Melnick
mesh_terms: D000565:Ameloblasts / Q000166:cytology; D000566:Amelogenesis; D000567:Amelogenesis Imperfecta / Q000196:embryology / Q000821:virology; D053523:Amelogenin / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003743:Dental Enamel / Q000002:abnormalities*; D003744:Dental Enamel Hypoplasia / Q000196:embryology / Q000821:virology; D003746:Dental Enamel Proteins / Q000096:biosynthesis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D051379:Mice; D008963:Molar / Q000196:embryology* / Q000502:physiology / Q000821:virology*; D009804:Odontoblasts / Q000166:cytology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D046509:Tissue Culture Techniques; D000099311:Dentin Sialophosphoprotein
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C507200:Amelx protein, mouse; C038456:tuftelin