Lu Xincheng, Rios Hector F, Jiang Baichun, Xing Lianping, Kadlcek Renata, Greenfield Edward M, Luo Guangbin, Feng Jian Q
Department of Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.
Eur J Oral Sci. 2009 Dec;117(6):625-35. doi: 10.1111/j.1600-0722.2009.00690.x.
A new spontaneous mouse mutant (ntl) with autosomal-recessive osteopetrosis was characterized. These mice formed tartrate-resistant acid phosphate (TRAP)-positive osteoclasts but their osteoclasts had no ruffled border and did not resorb bone. These mice displayed no tooth eruption or tooth root formation. Adult mutant mice developed odontoma-like proliferations near the proximal ends of the incisors. Intraperitoneal injection of progenitor cells from the liver of 16.5 days postcoitum wild-type embryos into newborn mutants rescued the osteopetrosis phenotype, indicating that the defects were intrinsic to the osteoclasts. Our findings not only provide further support for a critical role of osteoclasts in tooth eruption and tooth root development, but also suggest that the perturbation of the homeostasis of the odontogenic precursors of the incisors is primarily responsible for the development of the odontoma-like proliferations in this osteopetrosis mutant. Genetic mapping has narrowed down the location of the mutant allele to a genetic interval of 3.2 cM on mouse chromosome 17.
一种新的具有常染色体隐性骨硬化症的自发小鼠突变体（ntl）被鉴定出来。这些小鼠形成了抗酒石酸酸性磷酸酶（TRAP）阳性的破骨细胞，但它们的破骨细胞没有皱襞缘，也不吸收骨质。这些小鼠没有牙齿萌出或牙根形成。成年突变小鼠在门齿近端附近出现牙瘤样增殖。将妊娠16.5天野生型胚胎肝脏中的祖细胞腹腔注射到新生突变体中可挽救骨硬化症表型，这表明缺陷是破骨细胞固有的。我们的研究结果不仅进一步支持了破骨细胞在牙齿萌出和牙根发育中的关键作用，还表明门齿牙源性前体细胞内稳态的紊乱是这种骨硬化症突变体中牙瘤样增殖发展的主要原因。基因定位已将突变等位基因的位置缩小到小鼠17号染色体上3.2 cM的遗传区间。
