UNDERSTANDING THE EFFECTS OF THE HUMAN SLE-ASSOCIATED BANK1 MUTATIONS

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。 在以前的全基因组扫描中，我们确定BANK 1是一个与SLE易感性有关的基因。后续研究发现BANK 1的两种多态性与SLE风险特异性相关，并对BANK 1亚型的功能和表达产生影响。我们将致力于验证风险同种型通过破坏分子信号级联导致自身抗体产生增加的假设。将根据活化状态对B细胞进行分层，并在这些亚组中检测BANK 1表达水平，以确定任何相关性。

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. In a previous genome-wide scan, we identified BANK1 as a gene involved in susceptibility for SLE. Follow-up studies identified two polymorphisms in BANK1 that are specifically associated with SLE risk and which have an impact on the function and expression of BANK1 isoforms. We will work to test the hypothesis that the risk isoforms cause increased autoantibody production through disruption of molecular signaling cascades. B cells will be stratified according to their activation status and BANK1 expression levels will be tested in these subsets to identify any correlations.