Effect of the intestinal flora on amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy.
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.
Noguchi
Hiromitsu
H
Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, 4-24-1 Kuhonji, Kumamoto 862-0976.
Ohta
Mika
M
Wakasugi
Shoji
S
Noguchi
Kazuhiro
K
Nakamura
Naoko
N
Nakamura
Osamu
O
Miyakawa
Kazuhisa
K
Takeya
Motohiro
M
Suzuki
Misao
M
Nakagata
Naomi
N
Urano
Toru
T
Ono
Tomomichi
T
Yamamura
Ken-ichi
K
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
D000682:Amyloid