GENETICS OF BACTERIALLY-INDUCED ALVEOLAR BONE LOSS

描述(改编自调查者摘要)：牙周病 在成人中是一个重大的公共卫生负担。它是强烈的 与革兰氏阴性菌牙龈卟啉单胞菌有关 细菌本身并不能解释疾病中的种群差异。有一个 疾病发病率和严重程度的显著遗传因素。小鼠模型 在解剖各种不同的病原体方面被证明是非常有价值的 疾病。现代分子遗传学，包括数量性状座位(QTL) 分析，是解开遗传多态的有力工具 小鼠的各种疾病，包括易感性和 对传染病的抵抗力。小鼠基因组的很大一部分是 与人类基因组共享，从而鉴定和定位小鼠 基因座促进了人类对应物的发现。在当前的 在支持期间，首席调查员开发了一种老鼠模型，在该模型中 小鼠口腔感染P。 牙周炎。与杰克逊家族的德里·鲁布皮安博士合作 实验室，具有各种离散免疫缺陷的基因敲除小鼠 用于确定导致骨质流失的几个因素。《校长》 研究人员还发现，不同品系的免疫活性小鼠 不同的人在口腔感染后对骨丢失的敏感性不同。至F1 这些老鼠的杂交和回交，我们有初步证据表明 对牙龈假单胞菌引起的牙槽骨丢失的易感性和抵抗力 可遗传的特征。建议研究这一现象的遗传基础。 敏感性和抗药性。首先，病理生理过程 在这个符合骨丢失的小鼠模型中将进一步表征和 其他与骨丢失相关的表型生物标志物也将被开发出来。 其次，将使用QTL分析来识别染色体区域 与易感性和抵抗力有关。这些目标加在一起将提供 牙龈假单胞菌诱发牙槽骨病理生物学的更全面描述 损失，并将允许首席调查员映射所涉及的基因座和等位基因 在敏感性和抵抗力方面。在本次调查中培育的小鼠品系 将可供其他人学习。在这里获得的遗传学知识 极有可能对候选基因的鉴定做出贡献 在人类身上。

DESCRIPTION (adapted from the Investigator's abstract): Periodontal disease among adult humans is a significant public health burden. It is strongly associated with the gram-negative bacterium, Porphyromonas gingivalis, yet bacteria alone do not explain population variance in the disease. There is a notable genetic component to both disease incidence and severity. Mouse models have proven extremely valuable in dissecting the pathobiology of various diseases. Modern molecular genetics, including quantitative trait locus (QTL) analysis, is a powerful tool for unraveling the genetic polymorphisms underlying various diseases in the mouse, including susceptibility and resistance to infectious diseases. Large portions of the murine genome are shared with the human genome, so that identification and localization of murine loci have facilitated discovery of their human counterparts. During the current support period, the Principal Investigator has developed a mouse model in which alveolar bone loss is reliably induced in mice by oral infection with P. gingivalis. In collaboration with Dr. Derry Roopenian of The Jackson Laboratory, knockout mice with various discrete immunodeficiencies have been used to identify several factors that contribute to bone loss. The Principal Investigator has also found that different strains of immunocompetent mice differ in their susceptibility to bone loss after oral infection. Through F1 crosses and backcross of these mice, we have initial evidence that susceptibility and resistance to P. gingivalis- induced alveolar bone loss are heritable traits. It is proposed to study the genetic basis for this susceptibility and resistance. First, the pathophysiological processes that coincide with bone loss in this mouse model will be further characterized and other phenotypic biomarkers will be developed that correlate with bone loss. Second, QTL analysis will then be used to identify chromosomal regions associated with susceptibility and resistance. Together these aims will provide a fuller description of the pathobiology of P. gingivalis-induced alveolar bone loss and will allow the Principal Investigator to map loci and alleles involved in susceptibility and resistance. Mouse strains developed in this investigation will be available for others to study. Knowledge of the genetics gained here has a high likelihood of contributing to the identification of candidate genes in humans.