Investigation of Cancer Predisposition in Heterozygous Carriers of the ATM

患有人类遗传性疾病共济失调-毛细血管扩张症的人容易患癌症，他们的父母和亲属(携带者)也是如此，他们的父母和亲属(携带者)有一个缺陷的基因副本。这是一种多系统疾病，也以神经退化、免疫缺陷、不孕不育和对辐射极度敏感为特征。该项目旨在建立一种这种疾病的小鼠模型，以研究缺陷基因携带者对癌症的易感性。已经在一名乳腺癌患者身上描述了将被引入老鼠体内的特殊突变，并已证明它会干扰ATM蛋白的正常功能。小鼠模型预计将密切反映人类疾病，并将提供机会，监测杂合子携带者的癌症发展。这一模型有望证实在人类中的观察结果，并为了解患癌症的易感性提供资源。该模型还将解决暴露于低剂量辐射和患癌症风险的问题。

Individuals with the human genetic disorder ataxia-telangiectasia are prone to cancer development and so also are their parents and relatives (carriers) who have one defective copy of the gene. This is a multisystem disease that is also characterized by neurodegeneration, immunodeficiency, infertility and extreme sensitivity to radiation. This project is designed to generate a mouse model of this disease to investigate cancer susceptibility in carriers of the defective gene. The specific mutation to be introduced into the mouse has been described in a patient with breast cancer and it has been shown to interfere with the normal function of the ATM protein. The mouse model is expected to reflect closely the human disease and will provide the opportunity to monitor heterozygous carriers for the development of cancer. This model is expected to confirm the observations in humans and provide a resource to understand susceptibility to develop cancer. The model will also address the issue of exposure to low dose radiation and risk of developing cancer.