COBRE: U OF KANSAS MEDICAL CTR: NULL-MOUSE CORE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 为了确定各种核受体在本Cobre提出的项目中的作用，我们正在KUMC开发各种核受体缺失(基因敲除)小鼠的繁育群体。特定的核受体敲除小鼠将被用来确定基础基因表达水平和/或其他表型指标与这些核受体的存在或不存在之间的关系。目前我们有以下零克隆：PXR、AhR、PXR？、CAR、PPAR？、Nrf2、HNF1？和HNF4？对于本提案的项目，我们还需要获得和/或开发小水电、FXR和RXR？到目前为止，这些基因敲除小鼠和品系匹配的野生型小鼠的冷冻肝脏已经由Frank Gonzalez博士(PPAR，PPARGamma，HNF4é，FXR)、谢文(PXR，PXR/CAR双基因敲除)、David Mangelsdorf(LXR)、David Moore(CAR)、Marie Demay(VDR)、Douglas Forrest(TRbeta)和Henry Sucov(RARbeta)慷慨提供。我们需要保持现有的基因敲除小鼠群体的数量，以允许按需进行实验，并在需求出现时设计新的基因敲除或双基因敲除。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To determine the role of the various nuclear receptors in the projects proposed in this COBRE, we are developing breeding colonies at KUMC of various nuclear receptor null (knockout) mice. Specific nuclear receptor knockout mice will be employed to determine the relationship between basal gene expression level and/or other measures of phenotype and the presence or absence of these nuclear receptors. At the present time we have the following null colonies: PXR, AhR, PXR¿, CAR, PPAR¿, Nrf2, HNF1¿, and HNF4¿. For the projects of this proposal, we will also need to obtain and/or develop SHP, FXR, and RXR¿. So far, frozen livers of those knockout mice and strain matched wild-type mice have been generously provided by Drs. Frank Gonzalez (PPAR¿, PPARgamma, HNF4¿, FXR), Wen Xie (PXR, PXR/CAR double knockout out), David Mangelsdorf (LXR), David Moore (CAR), Marie Demay (VDR), Douglas Forrest (TRbeta), and Henry Sucov (RARbeta). We need to maintain our existing knockout mice colonies in numbers that permit experiments to be performed on demand, as well as engineer new knockouts or double knockouts as the needs arise.