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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.