Models of Autoimmune Disease--Genetically Defined Rabbit

在一个以开发一种或多种自身免疫性疾病模型为目标的特殊育种项目中，我们正在我们的群体中繁殖兔子，以研究对疾病诱导的易感性。我们最初的研究重点是人类系统性红斑狼疮（SLE）的兔子模型。众所周知，在人类中，一些基因影响对几种不同自身免疫性疾病的易感性。因此，选择性育种可能导致对自身免疫性疾病更广泛的易感性。SLE是一种复杂的慢性自身免疫性疾病，主要影响年轻女性。临床症状可能包括皮疹、关节炎、肾炎和神经系统紊乱（包括认知能力下降、癫痫发作、精神病）。SLE的特点是产生针对各种核抗原和双链DNA （dsDNA）的自身抗体。基于一些来自小鼠和狼疮患者的抗dna抗体与NR2谷氨酸受体交叉反应的报道，我们用多抗原肽骨架（BB）上的NMDA谷氨酸受体衍生肽免疫了兔组，并扩展了早期发表的报道，我们也用BB上的Sm B/B-引物衍生肽免疫了兔组。用这两种不同的肽免疫原免疫可产生抗dsdna抗体和其他与SLE相关的抗体。免疫前和免疫后血清的比较表明，一些MAP-peptide免疫兔的抗dsdna和抗核抗体水平升高。观察两个免疫组抗dsdna反应高的家兔出现癫痫发作。我们的研究证实了先前的一篇报道，即使用Sm肽免疫诱导非纯种家兔的slea样血清学，并将研究扩展到一种新的肽免疫原（Rai， G.等）。系统性红斑狼疮（SLE）模型：非近交系纯种兔肽免疫后的自身免疫（手稿正在准备中）。使用我们独特的纯种菌落将加快理解遗传易感性与暴露于确定的外部免疫原导致slea样表现的相互作用。目前的目标是通过评估组织病理学来继续这项工作；对前四组应答者相关的家兔进行免疫，繁育和扩大应答者相关家兔的数量（正在进行中）。

In a special breeding project with the goal of developing one or more models of autoimmune disease, we are breeding rabbits within our colony for susceptibility to disease induction. The initial focus of our study is a rabbit model of human Systemic Lupus Erythematosus (SLE). It is known that in man some genes affect susceptibility to several different autoimmune diseases. Thus selective breeding may result in broader susceptibility to autoimmune diseases. SLE is a complex, chronic autoimmune disorder that predominately affects young women. Clinical symptoms may include rash, arthritis, nephritis, and neurological disruption (including cognitive decline, seizures, psychosis). SLE is characterized by the production of autoantibodies to various nuclear antigens and double-stranded DNA (dsDNA). We immunized groups of rabbits with an NMDA glutamate receptor-derived peptide on a multiple antigen peptide backbone (BB) based on reports that some anti-DNA antibodies from mice and from lupus patients cross react with the NR2 glutamate receptor, and extending earlier published reports, we also immunized rabbits with an Sm B/B-prime-derived peptide on BB. Immunization with these two different peptide immunogens led to development of anti-dsDNA antibodies, and other correlates of human SLE. Comparisons of preimmune and post-immunization sera suggest that levels of anti-dsDNA and antinuclear antibodies have increased in some MAP-peptide immunized rabbits. Rabbits from both immunization groups with high anti-dsDNA responses were observed to experience seizures. Our studies confirm one earlier report that used Sm peptide immunization to induce SLE-like serology in non-pedigreed rabbits, and extend the studies to a new peptide immunogen (Rai, G. et al. Models of Systemic Lupus Erythematosus (SLE): Autoimmunity following peptide immunizations of non-inbred pedigreed rabbits-manuscript in preparation).The use of our unique pedigreed colony will expedite understanding the interactions of genetic susceptibility with exposure to defined external immunogens leading to SLE-like manifestations. Current objectives are to continue this work by evaluating tissue pathology; immunization of rabbits related to the first four groups of responders, and breeding and expanding the pool of related rabbits that are responders (in progress).