Virchows Archiv

, Volume 448, Issue 4, pp 463–471

Natural history of the Nihon (Bhd gene mutant) rat, a novel model for human Birt–Hogg–Dubé syndrome

  • Mami Kouchi
  • Kazuo Okimoto
  • Izumi Matsumoto
  • Kohji Tanaka
  • Masashi Yasuba
  • Okio Hino
Original Article

DOI: 10.1007/s00428-005-0142-9

Cite this article as:
Kouchi, M., Okimoto, K., Matsumoto, I. et al. Virchows Arch (2006) 448: 463. doi:10.1007/s00428-005-0142-9

Abstract

In the Nihon rat, an established model of hereditary renal cell carcinoma (RCC), the propensity for tumor development, is inherited as an autosomal dominant trait due to a single germline nucleotide insertion mutation in the rat Bhd ortholog. The Birt–Hogg–Dubé (BHD) syndrome is a rare autosomal dominant disease characterized by fibrofolliculoma, pulmonary cysts, spontaneous pneumothorax, and renal neoplasm. The renal lesions of the Nihon rat are characterized, and extrarenal lesions are also described in this work. The earliest lesion of the RCC was identified as an altered tubule at as early as 3 weeks of age and rapidly progressed through adenoma to carcinoma with the primary cell type being clear/acidophilic where some similarities were evident to RCCs in BHD syndrome. The Nihon rats demonstrate a heterotopic ossification within RCCs and three extrarenal lesions, clear cell hyperplasia/adenoma of the endometrium, clear cell change of the epithelium of striated portions of salivary glands, and cardiac rhabdomyomatosis. This rat model of hereditary RCC provides a useful tool for analyzing the series of events leading to renal tumorigenesis and for studying BHD gene functions.

Keywords

Birt–Hogg–Dubé syndrome Nihon rat Eker rat Renal cell carcinoma Extrarenal lesion 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Mami Kouchi
    • 1
  • Kazuo Okimoto
    • 1
  • Izumi Matsumoto
    • 1
  • Kohji Tanaka
    • 1
  • Masashi Yasuba
    • 1
  • Okio Hino
    • 2
  1. 1.Toxicology Group, Safety Research LaboratoriesDainippon Sumitomo Pharma Co., Ltd.SuitaJapan
  2. 2.Department of PathologyJuntendo University School of MedicineTokyoJapan

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