title: Identification of genetic loci affecting the establishment and development of Echinococcus multilocularis larvae in mice.
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)F(1) 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.
authors.affiliation: Department of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Kita 20, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakao
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kouguchi
authors.forename: Jun
authors.initials: J
authors.lastname: Matsumoto
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Dang
authors.forename: Ayo Yila
authors.initials: AY
authors.lastname: Simon
authors.forename: Daisuke
authors.initials: D
authors.lastname: Torigoe
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yuzaburo
authors.initials: Y
authors.lastname: Oku
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sugimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
authors.forename: Kinpei
authors.initials: K
authors.lastname: Yagi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004444:Echinococcosis, Hepatic / Q000235:genetics* / Q000469:parasitology*; D048210:Echinococcus multilocularis / Q000254:growth & development*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D007814:Larva / Q000254:growth & development; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D040641:Quantitative Trait Loci