title: Effect of the intestinal flora on amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy.
abstract: Familial amyloidotic polyneuropathy (FAP) is a hereditary disease characterized by the systemic accumulation of amyloid fibrils. A mutant transthyretin (TTR) gene is mainly responsible for the disease. However, the variable age of onset and low penetrance might be due to environmental factors, one of which is the intestinal flora. Three types of intestinal flora were introduced into a transgenic (Tg) mouse FAP model, 6.0-hMet30. The CV1 and CV2 group transgenic mice were transferred with the intestinal flora from two different mouse facilities housed under conventional conditions, and the SPF group transgenic mice were kept under specific pathogen free conditions in our facility. All the mice were maintained under controlled temperature, humidity and bacterial conditions. Over a period of 28 months, amyloid was not deposited in the SPF and CV1 groups. In contrast, amyloid was deposited in the esophagus and small intestine of two of the three CV2 mice at 18 months. Many neutrophils infiltrated the lesions. The numbers of tissue neutrophils were higher in the CV2 group than in the SPF and CV1 groups at 18 months. The CV2 flora included fewer gram-positive anaerobic cocci as well as higher proportions of yeasts, staphylococci and enterobacteriaceae compared with the SPF and CV1 flora. These findings suggest that the intestinal flora plays an important role in amyloid deposition.
authors.affiliation: Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, 4-24-1 Kuhonji, Kumamoto 862-0976.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Noguchi
authors.forename: Mika
authors.initials: M
authors.lastname: Ohta
authors.forename: Shoji
authors.initials: S
authors.lastname: Wakasugi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Noguchi
authors.forename: Naoko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakamura
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Miyakawa
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Misao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Toru
authors.initials: T
authors.lastname: Urano
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Ono
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamamura
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005766:Gastrointestinal Contents / Q000382:microbiology*; D051379:Mice; D008822:Mice, Transgenic; D013047:Specific Pathogen-Free Organisms
chemical_list: D000682:Amyloid