Japanese
 NBRP Rat No: 0217 Strain Name: UPL/Cas Commmon Name: UPL
 Principal Investigator  Toshinori Furukawa
 Organization   Hiroshima University 
 Address  

734-8551 Hiroshima

  Japan
 Telephone  082-257-5108  Fax:  082-257-5109  toshi@fumi.mayu.hiroshima-u.ac.jp
 Inbred Generations   F14+9 (Mar 2004) 
   
 Coat Color
 Deposition Status
 
 albino (c)
  Embryo      Sperm      Live Animals
 Usage Restrictions  In publishing, a citation of the following literature(s) designated by the DEPOSITOR is requested.
In publishing, an acknowledgment to the DEPOSITOR is requested. 
 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 Gja8: gap junction membrane channel protein alpha 8
 Origin Genetic analysis of the mutant showed that a single gene was semidominantly involved in the development of cataract. Homozygotes of UPL rats displayed early-onset cataract, which manifested as lens opacification before eye opening at 14 days of age and was often accompanied by microphthalmos and/or buphthalmos. Heterozygotes of UPL rats displayed late-onset cataract that started to appear at 2 to 4 weeks of age and developed into complete opacity of the lenses in both eyes (mature cataract) at 7 to 8 weeks of age. A candidate gene for formation of cataracts in UPL rats was mapped to rat chr 2, and a missense mutation (R340W) of the Cx50 (Gja8) gene was a strong candidate (Yamashita, 2002).
In UPL lenses, decreases in ATP content, increases in Ca<i>2+</i>ATPase mRNA and Ca<i>2+</i>ATPase activity, increase in the expression levels of interleukin-18 and interferon-γexistence of calpain-dependent proteolysis are recognized (Nabekura, 2004; Tomohiro, 1997; Nagai, 2007). Disulfiram, a powerful antioxidant, and aminoguanidine, an inhibitor of inducible NO synthase, can prevent lens opacification in UPL rats (Nabekuma, 2003; Nabekuma, 2004). The etiology of cataract in UPL rat is different from that in ICR rat (NBRP No.0290), and that in diabetic models (Nagai, 2008). The biological characteristics of UPL rats are considered to be normal except for the cataract. (Oct 7, 2010) 
 Strain Characteristics Genetic analysis of the mutant showed that a single gene was semidominantly involved in the development of cataract. Homozygotes of UPL rats displayed early-onset cataract, which manifested as lens opacification before eye opening at 14 days of age and was often accompanied by microphthalmos and/or buphthalmos. Heterozygotes of UPL rats displayed late-onset cataract that started to appear at 2 to 4 weeks of age and developed into complete opacity of the lenses in both eyes (mature cataract) at 7 to 8 weeks of age. A candidate gene for formation of cataracts in UPL rats was mapped to rat chr 2, and a missense mutation (R340W) of the Cx50 (Gja8) gene was a strong candidate (Yamashita, 2002). (Mar 3, 2009) 
 Breeding Conditions Maintained by rotation breeding of 3 groups (group A, B and C). Resulting heterozygoutes are used for breeding. Offspring born from group A×B are defined as group C, group B×C are defined as group A, group C×A are defined as group B. (Mar 3, 2009) 
 Genotyping  
 References  Tomohiro M, Maruyama Y, Yazawa K, Shinzawa S, Mizuno A.
The UPL rat: a new model for hereditary cataracts with two cataract formation types.
Exp Eye Res. 1993 Oct;57(4):507-10.

Tomohiro M, Aida Y, Inomata M, Ito Y, Mizuno A, Sakuma S.
Immunohistochemical study of calpain-mediated alpha-crystallin proteolysis in the UPL rat hereditary cataract.
Jpn J Ophthalmol. 1997 May-Jun;41(3):121-9.

Nabekura T, Koizumi Y, Nakao M, Tomohiro M, Inomata M, Ito Y.
Delay of cataract development in hereditary cataract UPL rats by disulfiram and aminoguanidine.
Exp Eye Res. 2003 Feb;76(2):169-74.

Nabekura T, Tomohiro M, Ito Y, Kitagawa S.
Changes in plasma membrane Ca2+ -ATPase expression and ATP content in lenses of hereditary cataract UPL rats.
Toxicology. 2004 Apr 15;197(2):177-83.

Nagai N, Ito Y.
Adverse effects of excessive nitric oxide on cytochrome c oxidase in lenses of hereditary cataract UPL rats.
Toxicology. 2007 Dec 5;242(1-3):7-15. Epub 2007 Sep 8.

Nagai N, Ito Y, Okamura H.
Involvement of interleukin 18 in cataract development in hereditary cataract UPL rats.
J Biochem. 2007 Nov;142(5):597-603.

Nagai N, Ito Y, Takeuchi N, Usui S, Hirano K.
Comparison of the mechanisms of cataract development involving differences in Ca2+ regulation in lenses among three hereditary cataract model rats.
Biol Pharm Bull. 2008 Nov;31(11):1990-5.