Epithelial-specific knockout of the Rac1 gene leads to enamel defects

Zhan Huang, Jieun Kim, Rodrigo Lacruz, Pablo Bringas, Michael Glogauer, Timothy Bromage, Vesa M. Kaartinen, Malcolm L. Snead

Research output: Contribution to journalArticle

Abstract

The Ras-related C3 botulinum toxin substrate 1 (Rac1) gene encodes a 21-kDa GTP-binding protein belonging to the RAS superfamily. RAS members play important roles in controlling focal adhesion complex formation and cytoskeleton contraction, activities with consequences for cell growth, adhesion, migration, and differentiation. To examine the role(s) played by RAC1 protein in cell-matrix interactions and enamel matrix biomineralization, we used the Cre/loxP binary recombination system to characterize the expression of enamel matrix proteins and enamel formation in Rac1 knockout mice (Rac1 -/-). Mating between mice bearing the floxed Rac1 allele and mice bearing a cytokeratin 14-Cre transgene generated mice in which Rac1 was absent from epithelial organs. Enamel of the Rac1 conditional knockout mouse was characterized by light microscopy, backscattered electron imaging in the scanning electron microscope, microcomputed tomography, and histochemistry. Enamel matrix protein expression was analyzed by western blotting. Major findings showed that the Tomes' processes of Rac1 -/- ameloblasts lose contact with the forming enamel matrix in unerupted teeth, the amounts of amelogenin and ameloblastin are reduced in Rac1 -/- ameloblasts, and after eruption, the enamel from Rac1 -/- mice displays severe structural defects with a complete loss of enamel. These results support an essential role for RAC1 in the dental epithelium involving cell-matrix interactions and matrix biomineralization.

Original languageEnglish (US)
Pages (from-to)168-176
Number of pages9
JournalEuropean Journal of Oral Sciences
Volume119
Issue numberSUPPL.1
DOIs
StatePublished - Dec 2011

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Gene Knockout Techniques
Dental Enamel
Ameloblasts
Knockout Mice
Cell Communication
rac1 GTP-Binding Protein
Unerupted Tooth
Electron Microscope Tomography
Keratin-14
Amelogenin
X-Ray Microtomography
Focal Adhesions
Cytoskeleton
Transgenes
GTP-Binding Proteins
Cell Adhesion
Genetic Recombination
Electron Microscopy
Tooth
Epithelium

Keywords

  • Ameloblast
  • Cell adhesion
  • Epithelial cell
  • Extracellular matrix
  • Rac1

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Epithelial-specific knockout of the Rac1 gene leads to enamel defects. / Huang, Zhan; Kim, Jieun; Lacruz, Rodrigo; Bringas, Pablo; Glogauer, Michael; Bromage, Timothy; Kaartinen, Vesa M.; Snead, Malcolm L.

In: European Journal of Oral Sciences, Vol. 119, No. SUPPL.1, 12.2011, p. 168-176.

Research output: Contribution to journalArticle

Huang, Z, Kim, J, Lacruz, R, Bringas, P, Glogauer, M, Bromage, T, Kaartinen, VM & Snead, ML 2011, 'Epithelial-specific knockout of the Rac1 gene leads to enamel defects', European Journal of Oral Sciences, vol. 119, no. SUPPL.1, pp. 168-176. https://doi.org/10.1111/j.1600-0722.2011.00904.x
Huang, Zhan ; Kim, Jieun ; Lacruz, Rodrigo ; Bringas, Pablo ; Glogauer, Michael ; Bromage, Timothy ; Kaartinen, Vesa M. ; Snead, Malcolm L. / Epithelial-specific knockout of the Rac1 gene leads to enamel defects. In: European Journal of Oral Sciences. 2011 ; Vol. 119, No. SUPPL.1. pp. 168-176.
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