Department of Prosthodontics, Faculty of Dental Medicine, Hadassah Medical Centers and The Hebrew University, Jerusalem, Israel.
BMC Genet. 2013 Aug 9;14:68. doi: 10.1186/1471-2156-14-68.
Periodontal infection (Periodontitis) is a chronic inflammatory disease, which results in the breakdown of the supporting tissues of the teeth. Previous epidemiological studies have suggested that resistance to chronic periodontitis is controlled to some extent by genetic factors of the host. The aim of this study was to determine the phenotypic response of inbred and Collaborative Cross (CC) mouse populations to periodontal bacterial challenge, using an experimental periodontitis model. In this model, mice are co-infected with Porphyromonas gingivalis and Fusobacterium nucleatum, bacterial strains associated with human periodontal disease. Six weeks following the infection, the maxillary jaws were harvested and analyzed for alveolar bone loss relative to uninfected controls, using computerized microtomography (microCT). Initially, four commercial inbred mouse strains were examined to calibrate the procedure and test for gender effects. Subsequently, we applied the same protocol to 23 lines (at inbreeding generations 10-18) from the newly developed mouse genetic reference population, the Collaborative Cross (CC) to determine heritability and genetic variation of control bone volume prior to infection (CBV, naïve bone volume around the teeth of uninfected mice), and residual bone volume (RBV, bone volume after infection) and loss of bone volume (LBV, the difference between CBV and RBV) following infection.
BALB/CJ mice were highly susceptible (P<0.05) whereas DBA/2J, C57BL/6J and A/J mice were resistant. Six lines of the tested CC population were susceptible, whereas the remaining lines were resistant to alveolar bone loss. Gender effects on bone volume were tested across the four inbred and 23 CC lines, and found not to be significant. Based on ANOVA analyses, broad-sense heritabilities were statistically significant and equal to 0.4 for CBV and 0.2 for LBV.
The moderate heritability values indicate that the variation in host susceptibility to the disease is controlled to an appreciable extent by genetic factors. These results strongly support the possibility of using the Collaborative Cross, as well as developing dedicated F2 (resistant x susceptible inbred strains) resource populations, for future dissection of genetic factors in periodontitis.
牙周感染（牙周炎）是一种慢性炎症性疾病，导致牙齿的支持组织受损。先前的流行病学研究表明，慢性牙周炎的抗性在一定程度上受到宿主遗传因素的控制。本研究旨在使用实验性牙周炎模型确定近交系和合作杂交（CC）小鼠群体对牙周细菌挑战的表型反应。在该模型中，将牙龈卟啉单胞菌和核梭杆菌共感染小鼠，这些细菌株与人类牙周病有关。感染 6 周后，采集上颌骨并使用计算机化微断层扫描（microCT）分析相对于未感染对照的牙槽骨丧失。最初，检查了四个商业近交系小鼠品系以校准程序并测试性别效应。随后，我们将相同的方案应用于新开发的小鼠遗传参考群体（合作杂交（CC））的 23 条系（近交世代 10-18），以确定感染前（CBV，未感染小鼠牙齿周围的固有骨量）、感染后（RBV，感染后骨量）和骨量损失（LBV，CBV 与 RBV 之间的差异）的控制骨量的遗传可遗传性和遗传变异。
BALB/CJ 小鼠高度易感（P<0.05），而 DBA/2J、C57BL/6J 和 A/J 小鼠则具有抗性。在测试的 CC 群体的 6 条系中易感，而其余系则对牙槽骨丧失具有抗性。在四个近交系和 23 条 CC 系中测试了性别对骨量的影响，发现没有显着影响。基于 ANOVA 分析，CBV 的广义遗传力具有统计学意义且等于 0.4，LBV 的广义遗传力等于 0.2。
中度遗传力值表明，宿主对疾病的易感性变化在很大程度上受到遗传因素的控制。这些结果强烈支持使用合作杂交以及开发专用 F2（抗性 x 易感近交系）资源群体来进一步解析牙周炎的遗传因素的可能性。
