title: Tooth enamel defects in mice with a deletion at the Arhgap 6/Amel X locus.
abstract: The amelogenin proteins regulate enamel mineral formation in the developing tooth. The human AMELX gene, which encodes the amelogenin proteins, is located within an intron of the Arhgap 6 gene. ARHGAP 6 encodes a Rho GAP, which regulates activity of Rho A, a small G protein involved in intracellular signal transduction. Mice were generated in which the entire ARHGAP 6 gene was deleted by Cre-mediated recombination, which also removed the nested Amel X gene. Enamel from these mice appeared chalky white, and the molars showed excessive wear. The enamel layer was hypoplastic and non-prismatic, whereas other dental tissues had normal morphology. This phenotype is similar to that reported for Amel X null mice, which have a short deletion that removed the region surrounding the translation initiation site, and resembles some forms of X-linked amelogenesis imperfecta in humans. Analysis of the enamel from the Arhgap 6/Amel X-deleted mice verifies that the Amel X gene is nested within the murine Arhgap 6 gene and shows that removal of the entire Amel X gene leads to a phenotype similar to the earlier Amel X null mouse results, in which no amelogenin protein was detected. However, an unusual layer of aprismatic enamel covers the enamel surface, which may be related to the 1.1-Mb deletion, which included Arhgap 6 in these mice.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors: S K
authors: SK
authors: Prakash
authors: C W
authors: CW
authors: Gibson
authors: J T
authors: JT
authors: Wright
authors: C
authors: C
authors: Boyd
authors: T
authors: T
authors: Cormier
authors: R
authors: R
authors: Sierra
authors: Y
authors: Y
authors: Li
authors: W R
authors: WR
authors: Abrams
authors: M A
authors: MA
authors: Aragon
authors: Z A
authors: ZA
authors: Yuan
authors: I B
authors: IB
authors: van den Veyver
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics; D053523:Amelogenin; D000818:Animals; D003743:Dental Enamel / Q000473:pathology*; D003746:Dental Enamel Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014070:Tooth / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C507199:AMELX protein, human; D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins; D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein