Towards Mapping Susceptibility Genes for Periodontitis Using Collaborative-Cross Mouse Population

Epidemiological studies in human have suggested that susceptibility to periodontal disease is controlled by host genetic factors. Recently, a highly genetically-diverse mouse population "The collaborative cross, (CC)" was initiated. This population serves as a resource powerful tool for dissecting the complexity of host susceptibility to infectious diseases. Objective: Define the phenotypic response of about 50 different lines of the CC mouse population to periodontitis and mapping QTL associated with host susceptibility to the disease. Methods: About 10 mice of each of 50 CC lines were assessed for their phenotypic response to periodontitis, and compared with uninfected mice of the same lines. . Briefly, infected mice were orally co-challenged with Porphyromonas gingivalis and Fusobacterium nucleatum. The infection was repeated three times at 2 day intervals. 42 days following the final infection, the maxillary jaws were harvested and alveolar bone volume was quantified using microCT. Results: Currently, we have completed the analysis of 23 different lines, which showed variation in response to the co-infection. Six lines out of the tested CC were susceptible, while the remaining lines were resistant. Basic bone volume of CC lines was significantly different. Sex effect of the mice on bone volume, was not to be significant. Broad-sense heritability of the bone volume trait of naïve mice and bone loss volume of mice due to infections was found to be 0.84 and 0.77, respectively. The analysis of the remaining 27 lines is ongoing. CC mice were genotyped with 620,000 SNP of mouse diversity array and QTL mapping will be performed on all the tested lines. Conclusion: Our results indicate that the variation in host susceptibility to the disease is mainly controlled by genetic factors, and support the suggestion of using the (CC) resource populations for dissection of the genetic background of host resistance to periodontitis