Identification of genetic loci affecting the establishment and development of Echinococcus multilocularis larvae in mice |
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Authors: | Nakao Ryo Kameda Yayoi Kouguchi Hirokazu Matsumoto Jun Dang Zhisheng Simon Ayo Yila Torigoe Daisuke Sasaki Nobuya Oku Yuzaburo Sugimoto Chihiro Agui Takashi Yagi Kinpei |
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Affiliation: | aDepartment of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Kita 20, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan;bLaboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan;cDepartment of Biological Science, Hokkaido Institute of Public Health, Kita 19, Nishi 12, Kita-ku, Sapporo, Hokkaido 060-0819, Japan;dLaboratory of Medical Zoology, Department of Veterinary Medicine, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan;eDepartment of Parasitology, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, 4-101 Koyama, Tottori 680-8553, Japan |
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Abstract: | Alveolar echinococcosis (AE) is a severe hepatic disorder caused by larval infection by the fox tapeworm Echinococcus multilocularis. The course of parasitic development and host reactions are known to vary significantly among host species, and even among different inbred strains of mice. As reported previously, after oral administration of parasite eggs, DBA/2 (D2) mice showed a higher rate of cyst establishment and more advanced protoscolex development in the liver than C57BL/6 (B6) mice. These findings strongly suggest that the outcome of AE is affected by host genetic factor(s). In the present study, the genetic basis of such strain-specific differences in susceptibility/resistance to AE in murine models was studied by whole-genome scanning for quantitative trait loci (QTLs) using a backcross of (B6 × D2)F1 and D2 mice with varying susceptibility to E. multilocularis infection. For cyst establishment, genome linkage analysis identified one suggestive and one significant QTL on chromosomes (Chrs.) 9 and 6, respectively, whereas for protoscolex development, two suggestive and one highly significant QTLs were detected on Chrs. 6, 17 and 1, respectively. Our QTL analyses using murine AE models revealed that multiple genetic factors regulated host susceptibility/resistance to E. multilocularis infection. Moreover, our findings show that establishment of the parasite cysts in the liver is affected by QTLs that are distinct from those associated with the subsequent protoscolex development of the parasite, indicating that different host factors are involved in the host–parasite interplay at each developmental stage of the larval parasite. Further identification of responsible genes located on the identified QTLs could lead to the development of effective disease prevention and control strategies, including an intensive screening and clinical follow-up of genetically high-risk groups for AE infection. |
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Keywords: | Echinococcus multilocularis Alveolar echinococcosis Zoonosis QTL Cyst Protoscolex Emcys1 Empsc1 |
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