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Specific pathogen free conditions prevent transthyretin amyloidosis in mouse models

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Abstract

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.

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Acknowledgements

We thank Mr. O. Nakamura and Ms. Michiyo Nakata for their technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a grant from the Osaka Foundation of Promotion of Clinical Immunology.

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Authors and Affiliations

  1. Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan

    Seiya Inoue, Mika Ohta, Zhenghua Li, Gang Zhao, Yutaka Takaoka & Ken-Ichi Yamamura

  2. Institute of Resource Development and Analysis, Kumamoto University, Honjo 2-2-1, Kumamoto, Japan

    Misao Suzuki

  3. Department of Pathology, Kumamoto University, Kumamoto, Japan

    Naomi Sakashita, Kazuhisa Miyakawa & Kiyoshi Takahashi

  4. Department of Orthopedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, 860-0811, Japan

    Yutaka Takaoka & Koji Takada

  5. Institute of Medical Science, University of Tokyo, Shiroganedai 4-6-1, Minato-ku, Tokyo, 108-8639, Japan

    Hajime Tei & Yoshiyuki Sakaki

  6. Laboratory Animal Unit, Research and Development Division, Takeda Chemical Industries, LTD, Himuro-cho 6-10-1, Takatsuki, Osaka, 569-1141, Japan

    Michio Masuoka

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  1. Seiya Inoue
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  2. Mika Ohta
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  9. Hajime Tei
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  14. Ken-Ichi Yamamura
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Correspondence to Ken-Ichi Yamamura.

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Seiya Inoue, Mika Ohta, and Zhenghua Li contributed equally to this work.

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Inoue, S., Ohta, M., Li, Z. et al. Specific pathogen free conditions prevent transthyretin amyloidosis in mouse models. Transgenic Res 17, 817–826 (2008). https://doi.org/10.1007/s11248-008-9180-9

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  • DOI: https://doi.org/10.1007/s11248-008-9180-9

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