Comparative Mouse Genomics Centers Consortiun

描述(摘自申请人？S摘要) 这个应用程序建议生产和分析已经被 被设计成表达细胞周期调节基因的减弱的等位基因。它 预计这些等位基因存在于人类群体中，但明显 主要是在环境挑战之后。细胞周期调控基因 将针对的是那些编码Cyclin D/CDK4，Rb， P14ink6复合体，它在细胞通过 细胞周期的G1期。最初的重点将放在细胞周期蛋白D1上 已知易患遗传性非息肉病的基因多态 结直肠癌(HNPCC)。这个项目将由克努森博士指导，他 是Rb和Cyclin D/CDK4复合体生物学方面的专家。一秒钟 该项目将由约兰达·桑切斯博士指导，重点是G2检查站 以及细胞周期调控基因Chk1。桑切斯博士？S的专长是酵母菌 遗传学以及控制细胞通过G2的机制 和M期。斯坦布鲁克博士是这笔赠款的首席研究员， 将指导第三个项目，该项目将培育出携带减毒等位基因的小鼠 Polo激酶，Plk3。该激酶与Chk1一样，具有G2/M调节功能 对DNA损伤有反应。辛辛那提大学理工学院 医学对机构核心设施做出了承诺，其中包括 一个小鼠转基因核心和一个小鼠基因敲除核心。这个核心就是建立起来的 由汤姆·多奇曼博士执导，他在这项提案中发挥了关键作用。 其他已建立的核心包括DNA合成和测序核心 由我们的内部咨询委员会成员乔安娜·格罗登博士撰写， 由Greg Boivin博士指导的比较病理学核心和生物统计学 核心。三个新的集成核心，部分由霍华德·休斯夫妇资助 医学院院长，还是孩子们？S 医院研究基金会，是可用的。其中包括一个DNA微阵列 核心，蛋白质组学核心，和生物信息学核心。此应用程序建议 利用这些核心设施并为集体做出贡献 调查人员在加深对 环境挑战与不同细胞周期基因间的相互作用 疾病的起源。

DESCRIPTION (Taken from the Applicant?s Abstract) This application proposes to produce and analyze mice that have been engineered to express attenuated alleles of cell cycle regulatory genes. It is anticipated that such alleles exist in human populations, but manifest predominantly after environmental challenge. The cell cycle regulatory genes that will be targeted are those encoding members of the Cyclin D/Cdk4, Rb, P14ink6 complex, which plays a critical role in the passage of cells through the G1 phase of the cell cycle. Initial emphasis will be given to a cyclin D1 polymorphism that is known to predispose to hereditary non-polyposis colorectal cancer (HNPCC). This project will be directed by Dr. Knudsen who is expert in the biology of Rb and the Cyclin D/Cdk4 complex. A second project, to be directed by Dr. Yolanda Sanchez, focuses on the G2 checkpoint and the cell cycle regulatory gene, Chkl. Dr. Sanchez?s expertise is in yeast genetics as well as in the mechanisms governing transit of cells through G2 and M phases. Dr. Stambrook is the principal investigator of this grant and will direct a third project that will produce mice with attenuated alleles of the Polo kinase, Plk3. This kinase, like Chkl, has G2/M regulatory function and is responsive to DNA damage. The University of Cincinnati College of Medicine has made commitments to institutional core facilities, which include a mouse Transgenic Core and a mouse knockout core. This core was established and is directed by Dr. Tom Doetschman, who plays a key role in this proposal. Other established cores include a DNA synthesis and sequencing core directed by Dr. Joanna Groden, a member of our internal advisory committee, a comparative pathology core directed by Dr. Greg Boivin, and a biostatistics core. Three new integrated cores funded, in part, by the Howard Hughes Medical Institute, by the Dean of the medical school, and by the Children?s Hospital Research Foundation, are available. These include a DNA microarray core, a proteomics core, and a bioinformatics core. This application proposes to take advantage of these core facilities and to contribute the collective expertise of the investigators in furthering the understanding of the interactions between environmental challenge and variant cell cycle genes in the genesis of disease.