Genotype is an important determinant factor of host susceptibility to periodontitis in the Collaborative Cross and inbred mouse populations

BMC Genetics

Fuad A Iraqi⁵  Yael Houri-Haddad⁴  Ervin I Weiss⁴  Richard Mott³  Asaf Wilensky²  Morris Soller¹  Aysar Nashef⁴  Yasser Salyma⁵  Ariel Shusterman⁴ 

[1] Department of Genetics, Hebrew University, Jerusalem, Israel;Department of Periodontology, Faculty of Dental Medicine, Hadassah Medical Centers and The Hebrew University, Jerusalem, Israel;Wellcome Trust Human Genome Centre, Oxford University, Oxford OX3 7BN, UK;Department of Prosthodontics, Faculty of Dental Medicine, Hadassah Medical Centers and The Hebrew University, Jerusalem, Israel;Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

关键词: Heritability;    Genes;    Collaborative cross;    microCT;    Experimental periodontitis;    Periodontal infection;   

Others  :  1086814
DOI  :  10.1186/1471-2156-14-68

 received in 2013-01-17, accepted in 2013-08-02,  发布年份 2013

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2013 Shusterman et al.; licensee BioMed Central Ltd.

【 图 表 】

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