Generation of Immunodeficient Rats With Rag1 and Il2rg Gene Deletions and Human Tissue Grafting Models
Generation of Immunodeficient Rats With Rag1 and Il2rg Gene Deletions and Human Tissue Grafting Models
复制标题
DOI：
10.1097/tp.0000000000002251
复制
发表时间：
2018-08-01
期刊：
影响因子：
6.2
通讯作者：
Anegon, Ignacio
中科院分区：
文献类型：
--
作者：
Menoret, Severine;Ouisse, Laure-Helene;Anegon, Ignacio
背景免疫缺陷小鼠是在缺乏适应性免疫应答的情况下分析潜在免疫原性分子的长期效应的宝贵工具。尽管如此，有模型和实验情况，将取代较大的免疫缺陷受体。大鼠非常适合进行需要较大尺寸的实验，并且仍然是适合啮齿动物设施的小动物模型。此外，大鼠比小鼠更能复制某些人类疾病，如强直性脊柱炎和杜兴氏病，这些疾病模型将大大受益于免疫缺陷大鼠，以测试不同的免疫原性治疗。IL 2 rg缺陷大鼠的免疫缺陷更严重，因为它们不仅部分缺乏T和B细胞，而且缺乏NK细胞。RRG动物表现出更严重的免疫抑制表型，因为它们表现出检测不到的T、B和NK细胞水平。同样，血清中所有免疫球蛋白同种型在Rag1或Il2rg缺陷大鼠中均降低，在Rag1和Il2rg（RRG）大鼠动物中检测不到。Rag1或Il2rg缺陷大鼠排斥同种异体皮肤移植和人类肿瘤，而动物不仅接受同种异体大鼠皮肤，而且接受异种人类肿瘤、皮肤和肝细胞。免疫人源化的RRG动物是successful.Conclusions，因此，免疫缺陷的RRG动物是有用的长期研究，其中免疫反应可能是一个障碍，包括不同组织的组织人源化的受体。
Background Immunodeficient mice are invaluable tools to analyze the long-term effects of potentially immunogenic molecules in the absence of adaptive immune responses. Nevertheless, there are models and experimental situations that would beneficiate of larger immunodeficient recipients. Rats are ideally suited to perform experiments in which larger size is needed and are still a small animal model suitable for rodent facilities. Additionally, rats reproduce certain human diseases better than mice, such as ankylosing spondylitis and Duchenne disease, and these disease models would greatly benefit from immunodeficient rats to test different immunogenic treatments.Methods We describe the generation of Il2rg-deficient rats and their crossing with previously described Rag1-deficient rats to generate double-mutant RRG animals.Results As compared with Rag1-deficient rats, Il2rg-deficient rats were more immunodeficient because they partially lacked not only T and B cells but also NK cells. RRG animals showed a more profound immunossuppressed phenotype because they displayed undetectable levels of T, B, and NK cells. Similarly, all immunoglobulin isotypes in sera were decreased in Rag1- or Il2rg-deficient rats and undetectable in Rats Rag1 and Il2rg (RRG) animals. Rag1- or Il2rg-deficient rats rejected allogeneic skin transplants and human tumors, whereas animals not only accepted allogeneic rat skin but also xenogeneic human tumors, skin, and hepatocytes. Immune humanization of RRG animals was unsuccessful.Conclusions Thus, immunodeficient RRG animals are useful recipients for long-term studies in which immune responses could be an obstacle, including tissue humanization of different tissues.