Specific pathogen free conditions prevent transthyretin amyloidosis in mouse models

• Published in: Transgenic research Vol. 17; no. 5; pp. 817 - 826
• Main Authors: Inoue, Seiya, Ohta, Mika, Li, Zhenghua, Zhao, Gang, Takaoka, Yutaka, Sakashita, Naomi, Miyakawa, Kazuhisa, Takada, Koji, Tei, Hajime, Suzuki, Misao, Masuoka, Michio, Sakaki, Yoshiyuki, Takahashi, Kiyoshi, Yamamura, Ken-Ichi
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01.10.2008; Springer Netherlands; Springer; Springer Nature B.V
• Subjects: Amyloidosis - metabolism; Amyloidosis - prevention & control; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biotechnology; Blotting, Western; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Genetic Engineering; Genetic technics; Life Sciences; Methods. Procedures. Technologies; Mice; Molecular Medicine; Original Paper; Plant Genetics and Genomics; Polymerase Chain Reaction; Prealbumin - metabolism; Transgenic animals and transgenic plants; Transgenics; Transgenic mouse; Environmental factor; Conventional conditions; Transthyretin-associated amyloidosis; Specific pathogen free conditions; Rodentia; Transgenic animal; Vertebrata; Mammalia; Mouse; Thyroxine binding prealbumin; Pathogenic; Amyloidosis; Models
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1007/s11248-008-9180-9

Transthyretin (TTR) associated amyloidosis is an autosomal dominant disorder characterized by peripheral and autonomic neuropathy. Both genetic and environmental factors are thought to be involved in development of TTR associated amyloidosis. Previously, we demonstrated that amyloid deposition was observed in various tissues of transgenic mouse lines carrying a human mutant TTR (Met30) gene. To analyze the influence of environmental factors on TTR amyloidosis, these amyloidogenic transgenic mouse models were kept under conventional (CV) or specific pathogen free (SPF) conditions. Although the serum levels of Met30 for mice housed in the CV and SPF conditions were similar, amyloid deposition was observed in CV conditions, but not in SPF conditions. In addition, the extent of amyloid deposition in transgenic mice was dependent on duration kept under CV conditions. There were significant differences in proportion of amyloid deposition in several tissues between CV and SPF conditions. Maintenance of these mice at 30°C did not induce amyloid deposition in SPF conditions. These results suggest that the SPF conditions can completely prevent amyloid deposition, and that environmental factors can affect the onset and progression even in a single gene disorder.