A functional genomic approach to the genetics of autoimmune (type A) gastritis

胸腺产生白血球，保护身体免受感染和癌症的侵袭。不幸的是，如果这些白细胞以人体自身组织为靶标，也会导致疾病。这些疾病被称为自身免疫性疾病，这种疾病的一个例子是自身免疫性(A型)胃炎，在这种疾病中，白细胞以胃的产酸细胞为靶标。由此造成的损害可能导致恶性贫血(维生素B12缺乏)和胃癌的发生。该项目研究了一种自身免疫性胃炎的小鼠模型，目的是确定在该模型中编码疾病易感性的基因。最终，这些信息应该有助于我们设计出可应用于临床情况的治疗方法。我们之前已经确定了导致这些小鼠胃炎的基因的位置。它们中的两个在一条染色体上非常接近，似乎非常重要，因为它们具有最强的影响。此外，有一些证据表明，这些基因也可能与糖尿病和狼疮的易感性有关。该项目旨在通过更准确地定位这些基因，并通过检查它们对正常情况下不容易患胃炎的小鼠的影响来进一步表征这些基因。

The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. This project studies a mouse model of autoimmune gastritis with the aim of identifying the genes that encode susceptibility to the disease in this model. Ultimately, this information should help us to devise therapies that can be applied to the clinical situation. We have previously identified the locations of the genes which are responsible for causing gastritis in these mice. Two of them are very close together on one chromosome and appear to be very important because they have the strongest effects. Furthermore, there is some evidence that these genes may also be involved in determining susceptibility to diabetes and lupus. This project aims to further characterise these genes by locating them more exactly and by examining their effect on mice not normally prone to gastritis.