Cystic cholangioma in the thoracic cavity of a rat.

A female congenic rat produced by repeated backcrossing of Nihon rats, a model for hereditary renal cell carcinoma, to Brown Norway rats was necropsied at 24 months of age. At necropsy, a white mass about 1 centimeter in size was observed in the thoracic cavity, and the mass partly adhered to the esophagus and the diaphragm. Histologically, the mass was clearly circumscribed by connective tissue, and consisted of neoplastic cuboidal epithelial cells that showed cystic tubular proliferation.

Hyaline glomerulopathy with tubulo-fibrillary deposits in young ddY mice.

Hyaline glomerulopathy with tubulo-fibrillary deposits was observed in two young female ddY mice. One of the mice showed gross systemic edema and bilateral enlargement and pale color of the kidneys, whereas no significant gross findings were noted in the other mouse. Microscopically, a large number of the glomeruli in both mice were enlarged because of diffuse and global deposition of amorphous eosinophilic materials.

The First Case of Feline Infectious Peritonitis-like Pyogranuloma in a Ferret Infected by Coronavirus in Japan.

A male ferret, which was purchased from abroad at 9 months of age, had shown significant weight loss starting at 13 months of age. The ferret subsequently showed decreasing motor activity and recumbency and was euthanized at 14 months of age. At necropsy, a white, quail egg-sized mass was found in the mesentery.

Serine 62 is a phosphorylation site in folliculin, the Birt-Hogg-Dubé gene product.

Recently, it was reported that the product of Birt-Hogg-Dubé syndrome gene (folliculin, FLCN) is directly phosphorylated by 5'-AMP-activated protein kinase (AMPK). In this study, we identified serine 62 (Ser62) as a phosphorylation site in FLCN and generated an anti-phospho-Ser62-FLCN antibody. Our analysis suggests that Ser62 phosphorylation is indirectly up-regulated by AMPK and that another residue is directly phosphorylated by AMPK.

Establishment and characterization of renal carcinoma cell lines from a Bhd gene mutant (Nihon) rat.

A germline insertion of a single nucleotide in the rat homologue of the human Birt-Hogg-Dubé (BHD) gene gives rise to dominantly inherited renal cell carcinoma (RCC) in the Nihon rat model. In this study, we established 7 lines (NR cell lines NR22, 24, 32, 45, 49, 54 and 64) from an RCC found in a Nihon rat. All cell lines consisted mainly of round or polygonal cells arranged in a cobblestone-like growth pattern.

Regulation of folliculin (the BHD gene product) phosphorylation by Tsc2-mTOR pathway.

The Birt-Hogg-Dubé gene (BHD) encodes the tumor suppressor protein folliculin (FLCN). The function of FLCN has recently been implicated in the regulation of rapamycin-sensitive mTOR complex (mTORC1). Reciprocally, the mTORC1-dependent phosphorylation of FLCN was reported.

Postoperative fibromatosis-type fibromas in the Bhd gene mutant (Nihon) rat.

Fibromatosis-type fibromas were found to develop at abdominal surgical sites in 4 heterozygous Nihon rats, a model for the human Birt-Hogg-Dubé syndrome. In all 4 rats, solitary and firm nodules were located within the lateral abdominal musculature involving the full thickness of the abdominal wall at the sites of laparotomy. Histologically, the nodules consisted of well-differentiated fibroblastic spindle-shaped cells.

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

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.

Genetic and environmental factors in hereditary predisposition to tumors: a conceptual overview.

Cancer is a heritable disorder of somatic cells. Carcinogenesis at the cellular level is like an opened Japanese fan, because initiated cells grow in several directions and tumors suggest the edge of the fan by having many gene abnormalities. We discuss here the primal force and gene networks (federal headship) in renal carcinogenesis.

Natural history of the Nihon rat model of BHD.

Hereditary cancer was first described in the rat by Eker and Mossige in 1954 in Oslo. The Eker rat model of hereditary renal carcinoma (RC) was the first example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal, and has been contributing to the elucidation of renal carcinogenesis. Recently, we found a second hereditary RC model in the Sprague-Dawley (SD) rat, in Japan in 2000, which was named the Nihon rat.

A germ-line insertion in the Birt-Hogg-Dubé (BHD) gene gives rise to the Nihon rat model of inherited renal cancer.

A rat model of hereditary renal carcinoma (RC) was found in a rat colony of the Sprague-Dawley strain in Japan and named the "Nihon" rat. In heterozygotes, RCs, predominantly the clear cell type, develop from early preneoplastic lesions, which began to appear as early as 3 weeks of age, to adenocarcinomas by the age of 6 months. The Nihon rat is an example of a Mendelian dominantly inherited predisposition for development of RCs like the Eker (Tsc2 gene mutant) rat.

Renal carcinogenesis: genotype, phenotype and dramatype.

Cancer is a heritable disorder of somatic cells. Environment and heredity are both important in the carcinogenic process. The Eker rat model of hereditary renal carcinoma (RC) is an example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal.