UNDERSTANDING THE EFFECTS OF THE HUMAN SLE-ASSOCIATED BANK1 MUTATIONS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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. 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. 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.