Prakash S K, Gibson C W, Wright J T, Boyd C, Cormier T, Sierra R, Li Y, Abrams W R, Aragon M A, Yuan Z A, van den Veyver I B
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Calcif Tissue Int. 2005 Jul;77(1):23-9. doi: 10.1007/s00223-004-1213-7. Epub 2005 Jul 14.
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.
釉原蛋白在牙齿发育过程中调节牙釉质矿化。编码釉原蛋白的人类AMELX基因位于Arhgap 6基因的一个内含子内。ARHGAP 6编码一种Rho GAP，它调节Rho A的活性，Rho A是一种参与细胞内信号转导的小G蛋白。通过Cre介导的重组产生了缺失整个ARHGAP 6基因的小鼠，这也删除了嵌套的Amel X基因。这些小鼠的牙釉质呈白垩色，磨牙显示出过度磨损。牙釉质层发育不全且无棱柱结构，而其他牙齿组织形态正常。这种表型与报道的Amel X基因敲除小鼠相似，后者有一个短缺失，去除了翻译起始位点周围的区域，并且类似于人类某些形式的X连锁釉质发育不全。对Arhgap 6/Amel X基因缺失小鼠的牙釉质分析证实，Amel X基因嵌套在小鼠Arhgap 6基因内，并表明去除整个Amel X基因会导致一种类似于早期Amel X基因敲除小鼠结果的表型，在早期结果中未检测到釉原蛋白。然而，一层异常的无棱柱牙釉质覆盖在牙釉质表面，这可能与1.1-Mb的缺失有关，该缺失在这些小鼠中包括Arhgap 6基因。
