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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 为了确定各种核受体在本COBRE中提出的项目中的作用，我们正在KUMC开发各种核受体缺失（敲除）小鼠的繁殖群体。 将采用特异性核受体敲除小鼠来确定基础基因表达水平和/或表型的其他测量与这些核受体的存在或不存在之间的关系。 目前，我们有以下空菌落：PXR，AhR，PXR <$，CAR，PPAR <$，Nrf 2，HNF 1 <$和HNF 4 <$。 对于本提案的项目，我们还需要获得和/或开发SHP、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由Frank Gonzalez（PPAR、FXR）、Wen Xie（PXR、PXR/CAR双敲除）、大卫Mangelsdorf（LXR）、大卫摩尔（CAR）、玛丽德迈（VDR）、道格拉斯福雷斯特（TRbeta）和亨利苏科夫（RAR beta）博士慷慨提供。 我们需要维持现有的基因敲除小鼠群体的数量，以允许根据需要进行实验，并根据需要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.