Functional studies of mutant nucleases in a genetic model of inflammatory and viral disease.

AGS与先天性风疹和巨细胞病毒感染等病毒性疾病非常相似。然而，它是由错误的基因而不是病毒感染引起的。我们最近发现了导致这种情况的几个基因。这些基因编码的酶称为核酸酶。核酸酶存在于身体的所有细胞中，它们的工作是将DNA和RNA分解成它们的组成部分。这些特殊的核酸酶与人体免疫反应的关系的发现是出乎意料的。可能是这些核酸酶清除了自然产生的“废物”DNA和RNA。这些基因的突变可能导致这一过程的失败，导致身体产生针对自身的免疫反应，从而模仿病毒感染的影响。这种免疫反应机制也与其他常见的自身免疫性疾病有关，例如lupus.We建议研究这些酶，以了解它们在细胞中的正常作用，并确定当这些酶由于AGS患者细胞中的基因突变而失败时会发生什么。这些研究将使我们更详细地了解自身免疫性疾病的过程以及人体如何对病毒感染作出反应。

Aicardi Goutihres Syndrome (AGS) closely resembles viral illnesses such as congenital rubella and cytomegalovirus infections. However it is caused by a faulty gene instead of viral infection. We have recently identified several genes that cause this condition. These genes encode enzymes called nucleases. Nucleases are found in all cells in the body and their job is to breakdown DNA and RNA into their component parts. The discovery of a relationship of these particular nucleases to the body's immune response was unexpected. It may be that these nucleases clean up naturally produced 'waste' DNA and RNA. Mutation in these genes could result in failure of this process, leading to the body mounting an immune reaction against itself, and so mimicking the effects of a viral infection. This immune response mechanism is also relevant to other common autoimmune diseases, such as lupus.We propose to study these enzymes to understand their normal roles in cells and to establish what happens when these enzymes fail due to gene mutations in AGS patient cells. These studies will provide us with a more detailed understanding of autoimmune disease processes and how the human body responds to viral infections.