Sec22b Knockout Mice Offer Novel Insights into Embryonic Development and Antigen Cross-Presentation

Abstract

The SNARE protein SEC22B contributes to a number of critical biological processes in a variety of cells. However, its functions have previously only been studied in vitro. We investigated SEC22B in vivo using four types of Sec22b transgenic mice: a Sec22b conditional gene-trap containing mouse, a Sec22b null allele containing mouse, and mice with Vav1-Cre and CD11c-Cre mediated Sec22b deletion. In deleting Sec22b from the whole organism using gene-trapped and null allele mice and from the hematopoietic system using Vav1-Cre, we uncover a previously undescribed function for Sec22b in mediating embryonic development before E8.5 and after E11.5. This was not explained by deletion of Sec22b in CD11c+ cells. Previously, SEC22B had been implicated as an essential mediator of antigen cross-presentation. Using CD11c-Cre Sec22bfl/fl mice with DC-specific deletion of Sec22b, we tested this function in vivo. We discovered that not only is Sec22b not necessary for cross-presentation in vivo or in vitro, but that previous cross-presentation phenotypes were due to off-target effects from the Sec22b shRNAs used. Collectively, these studies offer novel insights into the function of Sec22b in vivo, demonstrating that SEC22B is essential for embryogenesis but not for cross-presentation. Moreover, we show the limitations of drawing conclusions from in vitro work and shRNA silencing studies alone.