Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT, USA.
J Dent Res. 2013 Feb;92(2):173-9. doi: 10.1177/0022034512468157. Epub 2012 Nov 15.
Mice carrying a knock-in mutation (Phe377del) in the Ank gene replicate many skeletal characteristics of human craniometaphyseal dysplasia, including hyperostotic mandibles. Ank (KI/KI) mice have normal morphology of erupted molars and incisors but excessive cementum deposition with increased numbers of Ibsp- and Dmp1-positive cells on root surfaces. The cervical loops of adult Ank (KI/KI) lower incisors are at the level of the third molars, while they are close to the mandibular foramen in Ank (+/+) mice. Furthermore, Ank (KI/KI) incisors show decreased eruption rates, decreased proliferation of odontoblast precursors, and increased cell apoptosis in the stellate reticulum. However, their capability for continuous elongation is not compromised. Quantification of TRAP-positive cells in the apical ends of Ank (KI/KI) incisors revealed decreased osteoclast numbers and osteoclast surfaces. Bisphosphonate injections in Ank (+/+) mice replicate the Ank (KI/KI) incisor phenotype. These results and a comparison with the dental phenotype of Ank loss-of-function mouse models suggest that increased cementum thickness may be caused by decreased extracellular PPi levels and that the incisor phenotype is likely due to hyperostosis of mandibles, which distinguishes Ank (KI/KI) mice from the other Ank mouse models.
携带 ank 基因点突变（phe377del）的小鼠复制了许多人类颅骨-干骺端发育不良的骨骼特征，包括下颌骨骨质增生。ank（ki/ki）小鼠的萌出牙和切牙形态正常，但牙骨质过度沉积，根表面的 ibsp 和 dmp1 阳性细胞数量增加。成年 ank（ki/ki）下切牙的颈环位于第三磨牙水平，而 ank（+/+）小鼠的颈环靠近下颌孔。此外，ank（ki/ki）切牙的萌出率降低，成牙本质细胞前体的增殖减少，星状网状细胞的细胞凋亡增加。然而，它们的连续伸长能力没有受到影响。ank（ki/ki）切牙根尖部位 trpa 阳性细胞的定量分析显示破骨细胞数量和破骨细胞表面减少。在 ank（+/+）小鼠中注射双膦酸盐可复制 ank（ki/ki）切牙表型。这些结果与 ank 功能丧失型小鼠模型的牙齿表型比较表明，牙骨质厚度的增加可能是由于细胞外 ppi 水平降低所致，而切牙表型可能是由于下颌骨的骨质增生所致，这将 ank（ki/ki）小鼠与其他 ank 小鼠模型区分开来。
