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

Virchows Arch. 2006 Apr;448(4):463-71. doi: 10.1007/s00428-005-0142-9. Epub 2006 Jan 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / pathology
  • Animals
  • Blood Chemical Analysis
  • Body Weight / physiology
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Carcinoma, Renal Cell / ultrastructure
  • Disease Models, Animal*
  • Endometrial Hyperplasia / genetics
  • Endometrial Hyperplasia / pathology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Genetic Diseases, Inborn / genetics*
  • Germ-Line Mutation / genetics*
  • Heart Neoplasms / genetics
  • Heart Neoplasms / pathology
  • Hematologic Tests
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Kidney Neoplasms / ultrastructure
  • Male
  • Phenotype
  • Proteins / genetics*
  • Rats
  • Rats, Mutant Strains
  • Rhabdomyoma / genetics
  • Rhabdomyoma / pathology
  • Salivary Glands / pathology


  • Flcn protein, rat
  • Proteins