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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、慢性和复发性炎症性皮肤病，主要发生在儿童时期，但症状可以持续或在成年时开始。它也是成人职业性皮肤病最常见的原因。特应性皮炎与多种免疫异常和多种环境因素有关。动物模型是了解复杂疾病的基础和治疗方法的有力工具。NC/NGA近交系(NC)是1957年从日本花式小鼠中建立的，表现出自发性的严重皮炎。NC小鼠皮肤病变的表型与人类特应性皮炎的症状相匹配，如瘙痒、红斑和出血，并对各种过敏原产生高滴度的免疫球蛋白E(IgE)。在STAT6缺陷的NC同源基因小鼠中也观察到了类似的皮肤炎症，几乎没有IgE产生。遗传方法表明，许多遗传因素可能是导致皮肤炎症的原因。从基因上讲，NC品系属于家鼠群体，包括广泛使用的实验室菌株，如C57BL/6J。许多人试图确定与NC小鼠表现出的AD样皮肤病变有关的基因，但只发现了一个名为derm1的主要QTL基因座(Kohara等人。免疫遗传学，1991)。由于目前还没有确定NC小鼠自发性皮损的过敏原，而且除主效QTL外的其他QTL对该病的遗传效应很小，因此对该疾病的基因定位并不容易。我们尝试了另一种方法来鉴定疾病的细胞和遗传基础：这种方法被称为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。自然生物技术，2001)。我们将这种方法应用于去除可能导致NC小鼠皮肤损伤的细胞。这项研究目前仍在进行中。