The sodium bicarbonate cotransporter (NBCe1) is essential for normal development of mouse dentition.
Proximal renal tubular acidosis (pRTA) is a syndrome caused by abnormal proximal tubule reabsorption of bicarbonate resulting in metabolic acidosis. Patients with mutations to the SLC4A4 gene (coding for the sodium bicarbonate cotransporter NBCe1), have pRTA, growth delay, ocular defects, and enamel abnormalities. In an earlier report, we provided the first evidence that enamel cells, the ameloblasts, express NBCe1 in a polarized fashion, thereby contributing to trans-cellular bicarbonate transport. To determine whether NBCe1 plays a critical role in enamel development, we studied the expression of NBCe1 at various stages of enamel formation in wild-type mice and characterized the biophysical properties of enamel in NBCe1(-/-) animals. The enamel of NBCe1(-/-) animals was extremely hypomineralized and weak with an abnormal prismatic architecture. The expression profile of amelogenin, a known enamel-specific gene, was not altered in NBCe1(-/-) animals. Our results show for the first time that NBCe1 expression is required for the development of normal enamel. This study provides a mechanistic model to account for enamel abnormalities in certain patients with pRTA.
School of Dentistry, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.
Rodrigo S
RS
Lacruz
Antonio
A
Nanci
Shane N
SN
White
Xin
X
Wen
Hongjun
H
Wang
Sylvia F
SF
Zalzal
Vivian Q
VQ
Luong
Verna L
VL
Schuetter
Peter S
PS
Conti
Ira
I
Kurtz
Michael L
ML
Paine
D000818:Animals; D006863:Hydrogen-Ion Concentration; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000737:chemistry; D027982:Sodium-Bicarbonate Symporters / Q000737:chemistry / Q000378:metabolism*; D014070:Tooth / Q000196:embryology*; D055114:X-Ray Microtomography / Q000379:methods
D027982:Sodium-Bicarbonate Symporters; D012964:Sodium