Japanese
 NBRP Rat No: 0577 Strain Name: BHD/Dspe Commmon Name: Nihon rat, 遺伝性腎がん発症ラット
 Principal Investigator  Tadao Serikawa
 Organization   Graduate School of Medicine, Kyoto University Institute of Laboratory Animals
 Address  Yoshidakonoe-cho, Sakyo-ku

606-8501 Kyoto

  JAPAN
 Telephone  075-753-4360  Fax:  075-753-4409  serikawa@anim.med.kyoto-u.ac.jp
 Inbred Generations   F33+3 (April 2012) 
   
 Coat Color
 Deposition Status
 
 albino (c)
  Embryo      Sperm      Live Animals
 Usage Restrictions  In publishing, an acknowledgment to the DEPOSITOR is requested and the RECIPIENT of BIOLOGICAL RESOURCE shall obtain a prior written consent on use of it from the DEPOSITOR.
The RECIPIENT shall not resell, transfer or distribute of the BHD/Dspe rat to any third party for any kind of purpose. For researdh-only purposes, the RECIPIENT shall breed and multiply the BHD/Dspe rats. 
 Genetic Status   Inbred   Segregating   Congenic   Consomic    Recombinant 
  Coisogenic   Spont. Mutant    Transgene   Ind. Mutant    Others 
 Comercial Availability   
 Research Category   Diabetes Obesity    Neurobiology    Ophthalmology    Dentistry    Cardio- Hypertension 
  Oncology   Metabolism   Otorhinology    Immunology    Infectious Disease
  Osteology    Internal Medicine   Dermatology   Reproduction    Development
  Behavior    Hematology    Urology   Pharmacology   Others 
  Control Strains   Reporter gene Strains  
 Gene Flcn: folliculin
 Origin A rat showing hereditary renal cell carcinoma was found in a Jcl:SD rat colony in the Dainippon Pharmaceutical Co., Ltd. and named Nihon rat (Okimoto, 2000). Thereafter they have been maintained at Dainippon Sumitomo Pharma Co., Ltd.. BHD (Birt-Hogg-Dubé) rat. (Mar 23, 2010) 
 Strain Characteristics Hereditary renal cell carcinoma (RCC) model. A model rat for human Birt-Hogg-Dub&eacute; (BHD) syndrome, characterized by fibrofolliculoma, spontaneous pneumothorax and renal neoplasm. <br />
In heterozygous BHD rats, renal tumors appear macroscopically about 6 weeks of age. Histologically, preneoplastic lesions for RCCs are recognized from 3 weeks of age and it develops adenomas predominantly consisting of clear cells by 8 weeks (Hino, 2004). Besides RCCs, BHD rats demonstrate clear cell hyperplasia/adenoma of the endometrium, clear cell change of the epithelium of striated portions of salivary glands, and cardiac rhabdomyomatosis (Kouchi, 2006). <br />
The causative gene was mapped on rat chromosome 10 by Hino et al., 2001, and identified as nonsense mutation of <i>Flcn</i> (<i>Bhd</i>) gene by Okimoto et al., 2004. (Mar 23, 2010) 
 Breeding Conditions Maintained in heterozygous condition. Embryonic lethal in homozygous state. (Mar 23, 2010) 
 Genotyping Genotyping by sequencing analysis. A 1-bp insertion at exon 3 of <i>Flcn</i> (<i>Bhd</i>) gene on rat chromosome 10. BHD rats have an insertion of Flcn (Bhd). Please refer to reference 5 (Okimoto, 2004). Mutant rats can be recognized by the presence of the renal tumor on the surface of the kidney after 10 weeks of age. (Mar 23, 2010)

<a href="http://www.anim.med.kyoto-u.ac.jp/nbr/documents/PCR_Gene/Flcn_en.pdf">Genotyping protocol for Flcn</a> 
 References  1. Okimoto K, Kouchi M, Kikawa E, Toyosawa K, Koujitani T, Tanaka K, Matsuoka N, Sakurai J, Hino O.
A Novel ”Nihon” Rat Model of a Mendelian Dominantly Inherited Renal Cell Carcinoma
Jpn J Cancer Res 2000, 91, 1096-1099

2. 新規遺伝性腎癌ラット（Nihonラット）にみられる腫瘍性病変の発生時期に関する検討
日本疾患モデル学会誌 17, 16-19 (2001)

3. O Hino, K Okimoto, M Kouchi, J Sakurai.
A Novel Renal Carcinoma Predisposing Gene of the Nihon Rat Maps on Chromosome 10.
Jpn J Cancer Res 2001, 92, 1147-1149

4. Hino O, Kobayashi T, Momose S, Kikuchi Y, Adachi H, Okimoto K
Renal carcinogenesis: Genotype, phenotype and dramatype.
Cancer Sci. 2003 94:2 142-147

5. Okimoto K, Sakurai J, Kobayashi T, Mitani H, Hirayama Y, Nickerson ML, Warren MB, Zbar B, Schmidt LS, Hino O.
A germ-line insertion in the Birt-Hogg-Dub&eacute; (BHD) gene gives rise to the Nihon rat model of inherited renal cancer.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2023-7.

6. 樋野興夫、沖本一夫
腎癌モデル－Eker Rat & Nihon Rat－
ヒト疾患モデル: 難病の病態解明と診断・治療への応用 / 秦順一編集2004, 88-93

7. Kazuo Okimoto, Mami Kouchi, Izumi Matsumoto, Junko Sakurai, Toshiyuki Kobayashi, Okio Hino
Natural History of the Nihon Rat Model of BHD
Current Molecular Medicine, Volume 4, Number 8, December 2004 , pp. 887-893(7)

8. Togashi Y, Kobayashi T, Momose S, Ueda M, Okimoto K, and Hino O.
Transgenic rescue from embryonic lethality and renal carcinogenesis in the Nihon rat model by introduction of a wild-type Bhd gene.
Oncogene 25: 2885-2889, 2006

9. Hino O, Kobayashi T, Okimoto K
Genetic and environmental factors in hereditary predisposition to tumors: a conceptual overview
Cancer: Cell Structures, Carcinogens and Genomic Instability 2006:96 269-292

10. Kouchi M, Okimoto K, Matsumoto I, Tanaka K, Yasuba M, Hino O.
Natural history of the Nihon (Bhd gene mutant) rat, a novel model for human Birt-Hogg-Dub&eacute; syndrome.
Virchows Arch. 2006 Apr;448(4):463-71. Epub 2006 Jan 31.

11. Kouchi M, Okimoto K, Matsumoto I, Michimae Y, Yamada T, Inoue T, Kimura T, Seki T, Yasuba M, Hino O.
Postoperative fibromatosis-type fibromas in the Bhd gene mutant (Nihon) rat.
Exp Toxicol Pathol. 2008 Mar;59(5):273-9. Epub 2007 Nov 26.