Enamel pathology resulting from loss of function in the cystic fibrosis transmembrane conductance regulator in a porcine animal model

Cells Tissues Organs. 2011;194(2-4):249-54. doi: 10.1159/000324248. Epub 2011 Apr 28.

Abstract

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a phosphorylation- and ATP-regulated anion channel. CFTR expression and activity is frequently associated with an anion exchanger (AE) such as AE2 coded by the Slc4a2 gene. Mice null for Cftr and mice null for Slc4a2 have enamel defects, and there are some case reports of enamel anomalies in patients with CF. In this study we demonstrate that both Cftr and AE2 expression increased significantly during the rat enamel maturation stage versus the earlier secretory stage (5.6- and 2.9-fold, respectively). These qPCR data im- ply that there is a greater demand for Cl(-) and bicarbonate (HCO₃⁻) transport during the maturation stage of enamel formation, and that this is, at least in part, provided by changes in Cftr and AE2 expression. In addition, the enamel phenotypes of 2 porcine models of CF, CFTR-null, and CFTR-ΔF508 have been examined using backscattered electron microscopy in a scanning electron microscope. The enamel of newborn CFTR-null and CFTR-ΔF508 animals is hypomineralized. Together, these data provide a molecular basis for interpreting enamel disease associated with disruptions to CFTR and AE2 expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amelogenesis / genetics
  • Animals
  • Anion Transport Proteins / genetics
  • Anion Transport Proteins / metabolism
  • Antiporters / genetics
  • Antiporters / metabolism
  • Calcification, Physiologic / genetics
  • Cell Differentiation / genetics
  • Chloride-Bicarbonate Antiporters
  • Cystic Fibrosis Transmembrane Conductance Regulator / deficiency*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Dental Enamel / growth & development
  • Dental Enamel / pathology*
  • Dissection
  • Mice
  • Models, Animal*
  • Organ Specificity / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • SLC4A Proteins
  • Sus scrofa / metabolism*
  • Up-Regulation / genetics

Substances

  • Anion Transport Proteins
  • Antiporters
  • Chloride-Bicarbonate Antiporters
  • RNA, Messenger
  • SLC4A Proteins
  • Slc4a2 protein, mouse
  • Slc4a2 protein, rat
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator