Japanese
 NBRP Rat No: 0556 Strain NameAR-EdnrbSl/Okkm Commmon Name: Aganglionosis rat
 Principal Investigator  Tohru Kimura
 Organization   National Institute for Physiological Sciences Center for Experimental Animals
 Address  38 Nishigo-naka, Myodaiji, Okazaki

444-8585  Aichi

 Japan
 Telephone  0564-55-7882  Fax:  0564-55-7881  kimura@nips.ac.jp
 Inbred Generations    
   
 Coat Color
 Deposition Status
 
 black hooded
  Embryo      Sperm      Live Animals
 Usage Restrictions  In publishing, an acknowledgment to the DEPOSITOR is requested. 
 Genetic Status   Inbred   Segregating   Congenic   Consomic    Recombinant 
  Coisogenic   Spont. Mutant    Transgene   Ind. Mutant    Others closed colony
 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 Ednrb: endothelin receptor type B
 Origin Congenital megacolon rats were found in offspring of a female albino rat crossed with a wild male by Ikadai <i>et al.</i> at Institute for Animal Reproduction in 1973 and were named Aganglionosis Rat (AR) (Ikadai, 1979). (Jul 7, 2009) 
 Strain Characteristics AR rats are characterized by megacolon and white coat color with a small pigmented spot on the head (Ikadai, 1979). AR shows a long constricted segment of the intestine, which extended from the distal ileum to the rectum. Histologically, myenteric and submucosal plexus are absent. AR is considered to be an animal model of Hirshsprung’s disease. AR dies of an intestinal obstruction from 1 to 5 weeks of age. The autosomal recessive spotting lethal, <i>sl</i>, was revealed to be caused by a 301-bp interstitial deletion of Endothelin B receptor (Ednrb) (Ceccherini, 1995). (Jul 7, 2009) 
 Breeding Conditions Homozygous <i>sl</i> rats die within 1-5 weeks of age. The <i>sl</i> mutation is maintained in heterozygous condition (closed colony). (Jul 7, 2009) 
 Genotyping <a href="http://www.anim.med.kyoto-u.ac.jp/nbr/documents/PCR_Gene/Ednrb_sl_en.pdf">Genotyping protocol for Ednrb</a> 
 References  筏井洋、他
先天性 Aganglionosis rat (Hirschsprung 病rat) の発見とその遺伝学的研究
先天異常 19: 31-36, 1979
 
Horie, H., Ikadai, H., Iwasaki, I., Ide, G., Takahashi, H.
Pathologic studies on newly established cingenital aganglionosis rat in Japan.
日本小児外科学会雑誌 16: 27-38, 1980
 
Ikadai, H., Shimizu, K., Nakajyo, S., Imamichi, T., Sasaki, Y., Urakawa, N.
Responses of narrow segments of intestines in the congenital aganglionosis rat to various stimulants.
Nippon Heikatsukin Gakkai Zasshi. 18: 347-361, 1982
 
Horisawa, M., Isiguro, Y., Ito, T., Kato, K.
Distribution of nervous system-specific enolase (NSE) and S-100 protein in the gastrointestinal tract of congenital aganglionosis rat.
Nippon Heikatsukin Gakkai Zasshi. 21: 11-24, 1985
 
Nagahama, M., Ozaki, T., Hama, K.
A study of the myenteric plexus of the congenitalaganglionosis rat (spotting lethal).
Anat. Embryol. 171: 285-96, 1985
 
Goto, S., Gunter, M., Scherer, LR., Bloch, T., Grosfeld, JL.
Surgical treatment of total colonic aganglionosis: efficacy of aganglionic patch enteroplasty in the rat.
J. Ped. Surgery. 21: 601-607, 1986
 
Domoto, T., Oki, M., Gonda, T., Inoue, K., Ozaki, T.
Distribution of nerves containing vasoactive intestinal polypeptide-like immunoreactivity in rats with congenital aganglionosis of the colon.
Neurosci. Res. 4: 309-315, 1987
 
Hirose, R., Nada, O., Kawana,T., Goto, S., Taguchi, T., Toyohara, T., Ikeda, K.
An immunohistochemical study of somatostatin-containing nerves in the aganglionic colon of human and rat.
Acta Neuropathol. 78: 372-379, 1989.
 
Gonda, T. Oki, M.
Distribution of cholinergic and catecholaminergic nerves in the colon of the rat with aganglionosis.
Jikken Dobutsu. Exp. Anim. 40: 471-484, 1991
 
Hirose, R., Nada, O., Kawana, T., Suita, S.
The intramural pelvic nerves immunoreactive for calcitonin gene-relatedpeptide in the rectum of normal and aganglionosis rat.
Anatom. Embryol. 187: 37-44, 1993
 
Nagahama, M., Tsutsui, Y., Ozaki, T., Hama, K.
Myenteric and submucosal plexuses of the congenital aganglionosis rat (spotting lethal) as revealed by scanning electron microscopy.
Biol. Signals. 2: 136-145, 1993
 
Domoto, T., Zhang, WB., Tsumori, T., Oki, M.
Distribution of extrinsic enkephalin-containing nerve fibers in the rat rectum and their origin in the major pelvic ganglion.
J. Aut. Nerv. Sys. 49: 135-146, 1994
 
Ceccherini, I., Zhang, AL., Matera, I., Yang, G., Devoto, M., Romeo, G., Cass, DT.
Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat
Hum. Mol. Genet. 4: 2089-2096, 1995
 
Yanai, T., Yamataka, A., Nagaoka,I., Fujimoto, T., Nishiye, H., Yamashita, T., Miyano, T.
Quantitative analysis of synaptic vesicle proteins in the aganglionic colon in rats with congenital aganglionosis.
J. Ped. Gastroenterol Nutr. 20: 239-240, 1995
 
Watanabe, Y., Ito, T., Harada, T., Takahashi, M., Kobayashi, S., Ozaki, T., Nimura, Y.
Expression of ret proto-oncogene products in the hypoganglionic segment of the small intestine of congenital aganglionosis rats.
J. Ped. Surgery. 30: 641-645, 1995
 
Watanabe, Y., Ito, T., Harada, T., Kobayashi, S., Ozaki, T., Nimura, Y.
Spatial distribution and pattern of extrinsic nerve strands in the aganglionic segment of congenital aganglionosis: stereoscopic analysis in spotting lethal rats.
J. Ped. Surgery. 30: 1471-1476, 1995
 
Teramoto, M., Domoto, T., Tanigawa, K., Yasui, Y., Tamura, K.
Distribution of nitric oxide synthase-containing nerves in the aganglionic intestine of mutant rats: a histochemical study.
J Gastroenterol. 31: 214-223, 1996
 
Gariepy, CE., Cass, DT., Yanagisawa, M
Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.
Proc. Natl. Acad. Sci. USA. 93: 867-72, 1996
 
Gariepy, CE., Williams, SC., Richardson, JA., Hammer, RE., Yanagisawa, M.
Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.
J. Clin. Invest. 102: 1092-101, 1998
 
Karaki, H., Mitsui-Saito, M., Takimoto, M., Oda, K., Okada, T., Ozaki, T., Kunieda, T.
Lack of endothelin ETB receptor binding and function in the rat with a mutant ETB receptor gene.
Biochem. Biophys. Res. Commun. 222: 139-143, 1996
 
Kunieda, T., Kumagai, T., Tsuji, T., Ozaki, T., Karaki, H., Ikadai, H.
A mutation in endothelin-B receptor gene causes myenteric aganglionosis and coat color spotting in rats.
DNA Res. 3: 101-105, 1996
 
Watanabe, Y., Ito, T., Iino, S., Harada, T., Ando, H., Seo, T., Kobayashi, S., Ozaki T.
Unique spindle cells in the involved ileal segment of rats with congenital aganglionosis.
J. Ped. Surgery. 32: 1229-1233, 1997
 
Gariepy, CE., Williams, SC., Richardson, JA., Hammer, RE., Yanagisawa, M.
Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.
J. Clin. Invest. 102:1092-1101, 1998
 
Matsumura, Y., Kuro, T., Kobayashi, Y., Konishi, F., Takaoka, M., Wessale, JL., Opgenorth, TJ., Gariepy, CE., Yanagisawa M.
Exaggerated vascular and renal pathology in endothelin-B receptor-deficient rats with deoxycorticosterone acetate-salt hypertension.
Circulation 102: 2765-2773, 2000

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