MacDougall M
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles.
Proc Finn Dent Soc. 1992;88 Suppl 1:195-208.
Dentin phosphoprotein (DPP, phosphophoryn) is the major non-collagenous protein component of the dentin extracellular matrix. This highly acidic phosphorylated protein is solely expressed by ectomesenchymal-derived odontoblast cells of the tooth organ. Previous biochemical studies have suggested the absence of this protein associated with the human genetic disease dentinogenesis imperfecta (DGI) Types I and II. However, due to the normal degradation of human DPP during dentin maturation, it has not been possible to establish if these reported differences were due to changes in DPP expression or secondary degradation rates in DGI affected versus normal teeth. Recently, we have taken both a molecular and biochemical approach to address this problem. Molecular studies have utilized genetic linkage studies performed on several multi-generation informative DGI kindreds. These studies have determined linkage between DGI Types II and III and two markers localized to the long arm of human chromosome 4 in the region 4q11-4q21. The strategy used in our study was to map the DPP gene locus to the long arm of human chromosome 4, in the same region as DGI, using a DPP oligonucleotide probe and somatic hybrid cell lines. The results indicate DPP is not localized to any region of human chromosome 4. Our data indicates that a mutation within the DPP gene locus is not associated with DGI Types II or III. This data is supported by the identification of human DPP (95 kDa) within the dentin extracellular matrix of molars isolated from an affected DGI type II patient using a mouse anti-DPP antibody. However, this does not exclude the possibility that enzymes associated with DPP post-translational modifications (ie. phosphorylation or degradation) might be responsible for this genetic disease.
牙本质磷蛋白（DPP，磷磷蛋白）是牙本质细胞外基质的主要非胶原蛋白成分。这种高度酸性的磷酸化蛋白仅由牙器官中源自外间充质的成牙本质细胞表达。先前的生化研究表明，这种蛋白的缺失与人类遗传性疾病Ⅰ型和Ⅱ型牙本质发育不全（DGI）有关。然而，由于人类DPP在牙本质成熟过程中的正常降解，一直无法确定这些报道的差异是由于DPP表达的变化还是DGI患牙与正常牙齿中二级降解率的不同。最近，我们采用了分子和生化方法来解决这个问题。分子研究利用了对几个多代信息丰富的DGI家系进行的遗传连锁研究。这些研究确定了Ⅱ型和Ⅲ型DGI与位于人类染色体4长臂4q11 - 4q21区域的两个标记之间的连锁关系。我们研究中使用的策略是使用DPP寡核苷酸探针和体细胞杂交细胞系，将DPP基因座定位到人类染色体4的长臂上，与DGI位于同一区域。结果表明DPP并不定位于人类染色体4的任何区域。我们的数据表明，DPP基因座内的突变与Ⅱ型或Ⅲ型DGI无关。使用小鼠抗DPP抗体从一名Ⅱ型DGI患者的磨牙牙本质细胞外基质中鉴定出人类DPP（95 kDa），这一结果支持了我们的数据。然而，这并不排除与DPP翻译后修饰（即磷酸化或降解）相关的酶可能导致这种遗传疾病的可能性。
