Targeted overexpression of amelotin disrupts the microstructure of dental enamel
Rodrigo S. Lacruz, Yohei Nakayama, James Holcroft, Van Nguyen, Eszter Somogyi-Ganss, Malcolm L. Snead, Shane N. White, Michael L. Paine, Bernhard Ganss
Basic Science and Craniofacial Biology
We have previously identified amelotin (AMTN) as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel) gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL) and ameloblastin (AMBN) was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM) was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.
Published - Apr 23 2012
Agricultural and Biological Sciences(all)
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tooth enamel Agriculture & Biology 100%
Dental Enamel Medicine & Life Sciences 77%
Ameloblasts Medicine & Life Sciences 65%
microstructure Agriculture & Biology 63%
Microstructure Chemical Compounds 49%
Protein Chemical Compounds 30%
Amelogenin Medicine & Life Sciences 26%
Prismatic Crystal Chemical Compounds 26%
Lacruz, R. S., Nakayama, Y., Holcroft, J., Nguyen, V., Somogyi-Ganss, E., Snead, M. L., White, S. N., Paine, M. L., & Ganss, B. (2012). Targeted overexpression of amelotin disrupts the microstructure of dental enamel. PloS one, 7(4), [e35200]. https://doi.org/10.1371/journal.pone.0035200
Targeted overexpression of amelotin disrupts the microstructure of dental enamel. / Lacruz, Rodrigo S.; Nakayama, Yohei; Holcroft, James; Nguyen, Van; Somogyi-Ganss, Eszter; Snead, Malcolm L.; White, Shane N.; Paine, Michael L.; Ganss, Bernhard.
In: PloS one, Vol. 7, No. 4, e35200, 23.04.2012.
Lacruz, RS, Nakayama, Y, Holcroft, J, Nguyen, V, Somogyi-Ganss, E, Snead, ML, White, SN, Paine, ML & Ganss, B 2012, 'Targeted overexpression of amelotin disrupts the microstructure of dental enamel', PloS one, vol. 7, no. 4, e35200. https://doi.org/10.1371/journal.pone.0035200
Lacruz RS, Nakayama Y, Holcroft J, Nguyen V, Somogyi-Ganss E, Snead ML et al. Targeted overexpression of amelotin disrupts the microstructure of dental enamel. PloS one. 2012 Apr 23;7(4). e35200. https://doi.org/10.1371/journal.pone.0035200
Lacruz, Rodrigo S. ; Nakayama, Yohei ; Holcroft, James ; Nguyen, Van ; Somogyi-Ganss, Eszter ; Snead, Malcolm L. ; White, Shane N. ; Paine, Michael L. ; Ganss, Bernhard. / Targeted overexpression of amelotin disrupts the microstructure of dental enamel. In: PloS one. 2012 ; Vol. 7, No. 4.
@article{bcc645fcb7b04bf9b21698b68e1d90a1,
title = "Targeted overexpression of amelotin disrupts the microstructure of dental enamel",
abstract = "We have previously identified amelotin (AMTN) as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel) gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL) and ameloblastin (AMBN) was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM) was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.",
author = "Lacruz, {Rodrigo S.} and Yohei Nakayama and James Holcroft and Van Nguyen and Eszter Somogyi-Ganss and Snead, {Malcolm L.} and White, {Shane N.} and Paine, {Michael L.} and Bernhard Ganss",
doi = "10.1371/journal.pone.0035200",
journal = "PLoS One",
publisher = "Public Library of Science",
T1 - Targeted overexpression of amelotin disrupts the microstructure of dental enamel
AU - Lacruz, Rodrigo S.
AU - Nakayama, Yohei
AU - Holcroft, James
AU - Nguyen, Van
AU - Somogyi-Ganss, Eszter
AU - Snead, Malcolm L.
AU - White, Shane N.
AU - Paine, Michael L.
AU - Ganss, Bernhard
N2 - We have previously identified amelotin (AMTN) as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel) gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL) and ameloblastin (AMBN) was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM) was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.
AB - We have previously identified amelotin (AMTN) as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel) gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL) and ameloblastin (AMBN) was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM) was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.
U2 - 10.1371/journal.pone.0035200
DO - 10.1371/journal.pone.0035200
JO - PLoS One
JF - PLoS One