权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Identification of cells or cell lineage responsible for atopic dermatitis-like skin lesions in model mice for human diseases by means of TRECK method

通过 TRECK 方法鉴定人类疾病模型小鼠中特应性皮炎样皮肤病变的细胞或细胞谱系

基本信息

批准号：
14208098
负责人：
YONEKAWA Hiromichi
金额：
$ 27.87万
依托单位：
TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Atopic dermatitis (eczema : AD) is pruritic, chronic and relapsing inflammatory skin disease with predominantly childhood onset, but the symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. Atopic dermatitis is associated with various immunological abnormalities and multiple environmental factors. Animal models are powerful tools to understand the bases and therapy of complex diseases. The NC/Nga inbred strain (NC), established from Japanese fancy mice in 1957, exhibits spontaneous severe dermatitis. The phenotypes of skin lesions in NC mice match the symptoms of the human atopic dermatitis, such as itching, erythema and hemorrhage with high titers of immunogloblin E (IgE) for various allergens. A similar skin inflammation has been observed in Stat6 deficient NC congenic mice with practically no IgE production. Genetic approaches indicate that numerous inherited factors can be responsible for the induction of skin inflammation. Genetically, the NC strain belongs to the Mus musculus domesticus group, which includes widely used laboratory strains, such as C57BL/6J.Many attempts has been made to identify genes responsible for the AD-like skin lesions shown by NC mice, and only one major QTL locus named derm1 has been identified (Kohara et al. Immunogenetics, 1991). The locus identification is not so easy because any allergens for the spontaneous skin lesions of NC mice have not been identified so far and other QTLs than the major one showed little genetic effects for the disease. We tried to do an alternative method for identification of cellular and genetic bases of the diseases : the method is called TRECK (Toxin-Receptor Mediated Cell Knockout) method. The TRECK method has been developed by Kohno and his collaborators (Saito et al. Nature Biotech, 2001). We applied this method to deplete cells possibly responsible for the skin lesions of NC mice. The research is now still in progress.

特应性皮炎（湿疹：AD）是一种瘙痒性、慢性和复发性炎症性皮肤病，主要在儿童时期发病，但症状可能持续或在成年后开始。它也是成人职业性皮肤病的最常见原因。特应性皮炎与多种免疫异常和多种环境因素有关。动物模型是理解复杂疾病的基础和治疗的有力工具。NC/Nga近交系（NC），建立于1957年从日本花式小鼠，表现出自发性严重皮炎。NC小鼠皮肤病变的表型与人类特应性皮炎的症状相匹配，例如瘙痒、红斑和出血，对于各种过敏原具有高滴度的免疫球蛋白E（IgE）。在Stat 6缺陷型NC同类小鼠中观察到类似的皮肤炎症，几乎没有IgE产生。遗传学方法表明，许多遗传因素可能导致皮肤炎症的诱导。在遗传学上，NC品系属于Mus musculus arteriticus组，其包括广泛使用的实验室品系，如C57 BL/6 J。已经进行了许多尝试来鉴定NC小鼠显示的AD样皮肤病变的基因，并且仅鉴定了一个名为derm 1的主要QTL位点（Kohara等，Immunogenetics，1991）。由于迄今为止还没有发现任何引起NC小鼠自发性皮肤病变的过敏原，并且除主要QTL外，其他QTL对疾病的遗传效应很小，因此位点的鉴定并不容易。我们试图做一种替代方法来鉴定疾病的细胞和遗传基础：该方法被称为TRECK（毒素受体介导的细胞敲除）方法。TRECK方法是由Kohno和他的合作者开发的（Saito等人，Nature Biotech，2001）。我们应用这种方法来去除可能导致NC小鼠皮肤病变的细胞。目前研究仍在进行中。