Genetic architecture of host response to tickborne disease in Peromyscus leucopus

项目总结(行政副刊) 对于行政补充，项目增加了第四个具体目标：功能性 自然发生的遗传变异对伯氏疏螺旋体反应的影响。 母项目主要需要采用先进的遗传学方法来识别特征，并最终 描述白脚鹿鼠作为主要储藏者的能力的机制 几种人畜共患病病原体，包括莱姆病的原因，同时在存在的情况下保持健康 持续性感染。到目前为止，在该项目的过程中，我们已经取得了一些发现，证明了一系列新的 采取反向遗传学方法的调查。这些发现既是先天的，也是后天的。 白假单胞菌种群NOS2基因的结构变异 这可能是感染期间一氧化氮和活性氮类产生减少的原因。(2) 在Permyscus中发现编码高亲和力Ig G Fc受体蛋白的失活Fcgr1基因 巨噬细胞和其他吞噬细胞(FcγR1或CD6 4)。(3)MHC II类基因之间的关联 伯氏疏螺旋体OspA蛋白的抗体应答。新的目标包括四个子目标- 目的：(A)白念珠菌NOS2基因及其3‘-非编码区变异体的宿主反应表型，(B)功能性 Permyscus突变株Fcgr1的作用，(C)MHC II基因变异和OspA抗体 免疫，以及(D)高通量发现和注释分离在 殖民地。这项由行政副刊支持的新研究预计将既有基本的 研究和翻译研究和应用的影响。这一发现也可能指导临床研究 莱姆病和其他壁虱传播感染患者的持续性疾病。

PROJECT SUMMARY (Administrative supplement) For the administrative supplement a fourth specific aim is added to the project: Functional consequences of naturally-occurring genetic variants for responses of Peromyscus to Borreliella burgdorferi. The parent project principally entails forward genetics approaches to identify the traits and ultimately characterize the mechanisms for the white-footed deermouse's capacity to serve as a major reservoir for several zoonotic agents, including the cause of Lyme disease, while maintaining fitness in the presence of persistent infection. In the course of the project to date, we have made discoveries that justify a new line of investigation that takes a reverse genetics approach. The discoveries represent both innate and aquired immunity in Peromyscus immunity: (1) Structural variants in the Nos2 gene of P. leucopus populations that could account for an attenuated production of nitric oxide and reactive nitrogen species during infection. (2) Evidence in Peromyscus of an inactivated Fcgr1 gene that encodes the high-affinity IgG Fc receptor protein (FcγR1 or CD64) of macrophages and other phagocytes. (3) An association between a MHC class II gene and the antibody response to the OspA protein of Borreliella burgdorferi. The new aim comprises four sub- aims: (A) host response phenotypes of variants of the Nos2 gene and its 3’-UTR in P. leucopus, (B) functional effects of mutant Fcgr1 of Peromyscus, (C) variation of MHC II genes and antibodies to OspA after immunization, and (D) high-throughput discovery and annotation of structural variants segregating in the colony. The new research supported by this administrative supplement is anticipated to have both basic research and translational research and application impacts. The findings may also guide clinical research on persisting illness in patients with Lyme disease and other tickborne infections.