Establishment of a Set of Combined Immunodeficient DA/Slc-Foxn1 super(rnu) Lyst super(bg) Congenic Rat Strains

• Published in: Experimental animals Vol. 53; no. 5; pp. 399 - 407
• Main Authors: Masui, Norio, Nishikawa, Tetsu, Takagi, Yumie, Kimura, Hiromitsu, Mori, Masayuki, Yokose, Shigeo, Asai, Hidekazu, Gonda, Toshihiko, Yanabe, Makoto, Sato, Katsunori
• Format: Journal Article
• Language: English
• Published: 01-01-2004
• ISSN: 1341-1357; 1881-7122
• DOI: 10.1538/expanim.53.399

The congenitally athymic nude rat is used for studying cancer and transplantation owing to its hairlessness and T-cell defective function caused by the Foxn1 super(rnu) gene. However, NK cell activity of the nude rat is markedly increased. It is known that NK cells play a major role in rejection of xenografts and in cytotoxicity against tumor cells. Thus, the athymic nude rat with impaired NK cell activity should be a useful model for extensive studies. The DA-Lyst super(bg)/Lyst super(bg) rat, a model for human Chediak-Higashi syndrome (CHS) is characterized by diluted-coat color and impairment of NK cell activity. We planned to establish a combined immunodeficient double mutant rat introgressed with the Foxn1 super(rnu) and Lyst super(bg) genes and a set of congenic strains having an identical genetic backgrounds simultaneously. Based on the phenotypic and genetic characteristics of the parental rat strains, the new strains were produced using continuous backcross and diagnosis with molecular genetic techniques. Each disease gene was diagnosed with PCR-RFLP or the long-nested PCR method. Furthermore, we used a marker- assisted congenic strategy based on scanning the genetic backgrounds of the parental rats with 461 rat microsatellite markers. We think that the newly established DA/Slc-Foxn1 super(rnu)/Foxn1 super(rnu) Lyst super(bg)/Lyst super(bg) double mutant will be useful as a severe disease model for human CHS, and the set of DA/Slc-Foxn1 super(rnu) Lyst super(bg) congenic strains which have impaired NK cell activity and/or defective T cell function should be useful for studying in cancer research, xenotransplantation, immune function and other wide-ranging studies.