title: Novel Helicobacter species H.japonicum isolated from laboratory mice from Japan induces typhlocolitis and lower bowel carcinoma in C57BL/129 IL10-/- mice.
abstract: A novel Helicobacter species Helicobacter japonicum was isolated from the stomach and intestines of clinically normal mice received from three institutes from Japan. The novel Helicobacter sp. was microaerobic, grew at 37°C and 42°C, was catalase and oxidase positive, but urease negative. It is most closely related to the 16S rRNA gene of H.muridarum (98.6%); to the 23S rRNA gene of H.hepaticus (97.9%); to the hsp60 gene of H.typhlonius (87%). The novel Helicobacter sp. has in vitro cytolethal distending toxin (CDT) activity; its cdtB gene sequence has 83.8% identity with that of H.hepaticus The whole genome sequence of H.japonicum MIT 01-6451 has a 2.06-Mb genome length with a 37.5% G + C content. When the organism was inoculated into C57BL/129 IL10-/-mice, it was cultured from the stomach, colon and cecum of infected mice at 6 and 10 weeks post-infection. The cecum had the highest H.japonicum colonization levels by quantitative PCR. The histopathology of the lower bowel was characterized by moderate to severe inflammation, mild edema, epithelial defects, mild to severe hyperplasia, dysplasia and carcinoma. Inflammatory cytokines IFNγ, TNFα and IL17a, as well as iNOS were significantly upregulated in the cecal tissue of infected mice. These results demonstrate that the novel H.japonicum can induce inflammatory bowel disease and carcinoma in IL10-/-mice and highlights the importance of identifying novel Helicobacter spp. especially when they are introduced from outside mouse colonies from different geographic locations.
authors.affiliation: Division of Comparative Medicine.
authors.forename: Zeli
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Division of Comparative Medicine.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Comparative Medicine.
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Muthupalani
authors.affiliation: Division of Comparative Medicine.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sheh
authors.affiliation: Division of Comparative Medicine.
authors.forename: Lenzie E
authors.initials: LE
authors.lastname: Cheaney
authors.affiliation: Division of Comparative Medicine.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Kaufman
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and.
authors.forename: Guanyu
authors.initials: G
authors.lastname: Gong
authors.affiliation: The Forsyth Institute, Cambridge, MA 02139, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Paster
authors.affiliation: Division of Comparative Medicine, jgfox@mit.edu.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and.
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000382:microbiology* / Q000473:pathology; D016998:Helicobacter / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000382:microbiology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D007564:Japan; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D053706:Typhlitis / Q000382:microbiology / Q000473:pathology
chemical_list: C000611649:IFNG protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse