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

机译:免疫缺陷的DA / Slc-Foxn1〜(rnu)Lyst〜(bg)同基因大鼠联合菌株的建立

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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~(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~(bg)/Lyst~(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~(rnu) and Lyst~(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~(rnu)/Foxn1~(rnu) Lyst~(bg)/Lyst~(bg) double mutant will be useful as a severe disease model for human CHS, and the set of DA/Slc-Foxn1~(rnu) Lyst~(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.
机译:由于无毛和Foxn1〜(rnu)基因引起的T细胞功能缺陷,先天性无胸腺裸鼠被用于研究癌症和移植。然而,裸鼠的NK细胞活性明显增加。已知NK细胞在异种移植的排斥和对肿瘤细胞的细胞毒性中起主要作用。因此,NK细胞活性受损的无胸腺裸鼠应成为广泛研究的有用模型。 DA-Lyst_(bg)/ Lyst_(bg)大鼠是人类Chediak-Higashi综合征(CHS)的模型,其特征是被毛颜色稀释和NK细胞活性受损。我们计划建立一个结合了Foxn1〜(rnu)和Lyst〜(bg)基因以及一组具有相同遗传背景的同系菌株的免疫缺陷型双重突变大鼠。根据亲本大鼠品系的表型和遗传特性,使用连续回交和分子遗传学诊断方法生产新品系。使用PCR-RFLP或长嵌套PCR方法诊断每种疾病基因。此外,我们基于461个大鼠微卫星标记物扫描亲本大鼠的遗传背景,使用了标记物辅助的同基因策略。我们认为,新建立的DA / Slc-Foxn1〜(rnu)/ Foxn1〜(rnu)Lyst〜(bg)/ Lyst〜(bg)双突变体将作为人CHS的严重疾病模型有用, NK细胞活性受损和/或T细胞功能缺陷的DA / Slc-Foxn1〜(rnu)Lyst〜(bg)同系菌株应用于癌症研究,异种移植,免疫功能和其他广泛研究。

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