The Study of MASPs Knockout Mice

Abstract

Plasma proteases, e.g. thrombin, factor X, complement factor D and C1s are responsible for the physiological activities, such as coagulation and complement system. These proteases circulate as their zymogen in blood and are activated by various stimulations. In this chapter, we focus on a family of plasma serine proteases, called MASP (MBL/ficolinassociated serine protease) that can activate the complement. Three distinct MASP, MASP-1, MASP-2 and MASP-3 have been identified in many species of vertebrates. Although the contribution of MASP-2 in activation of complement was well defined, the substrates for MASP-1 and MASP-3 were still obscure. We have generated MASP-1and MASP-3-deficient mice (Masp1/3-/-) to verify roles of MASP-1 and MASP-3 proteases in vivo. One major finding is that MASP-1, considered being a lectin pathway component—also acts as a pro-factor D (Df) convertase, the initiator of the alternative pathway. Our results emphasize a unique feature of MASP-1, participating two complement pathways. We also generated MASP-2 deficient mice. In here, we would like to summarize the results obtained from these knockout mice.