LEC rats: An overview of recent findings

✍ Scribed by Eiji Miyoshi; Junichi Fujii; Norio Hayashi; Naoyuki Taniguchi

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 94 KB
• Volume: 10
• Category: Article
• ISSN: 0896-548X
• DOI: 10.1002/(sici)1520-670x(1997)10:2<135::aid-jtra11>3.0.co;2-s

✦ Synopsis

The Long Evans rat with a cinnamon-like coat color, (LEC) rat established from a closed colony of the Long-Evans strain, spontaneously develops hepatitis as a result of abnormal copper accumulation in the liver and, eventually, hepatoma after 1 year of age. Numerous studies using the LEC rat as an animal model of Wilson's disease and hepatocarcinogenesis have been reported. Recently, the causative gene for abnormal copper accumulation, which is a rat homologue of the human Wilson's disease gene, was cloned and the defect of the gene was demonstrated. Therefore, the LEC rat represents a bona fide model of Wilson's disease from a genetic point of view. Moreover, other abnormalities such as immunodeficiency also have been found in the LEC rat. Incomplete maturation of T cells is observed in LEC rats, but the underlying mechanism for this remains unknown. Thus, LEC rats can be used as an ideal animal model for at least two different purposes. One is based on the defect in the gene responsible for the copper transporting ATPase (Atp7b), and, therefore, the investigation of LEC rats can provide useful information on the pathophysiology of Wilson's disease and lead to possible gene therapy. The other is triggered by abnormally accumulated copper and iron and/or a defect in the immune system. Free copper and iron accumulation, especially, may facilitate Fenton chemistry to produce reactive oxygen species, which represent likely candidates for carcinogenesis. Here, we review recent studies concerning the LEC rat from both genetic and biochemical points of views and propose perspectives for future investigations. J. Trace Elem. Exp. Med. 10:135-145, 1997.