Physiological Role of Mysterin/RNF213 in Zebrafish

Mysterin, also known as RNF213, is a very large intracellular protein of 591 kDa with unknown function. Long-standing genetic analyses ultimately revealed that its C-terminal mutation (R4810K) is the key genetic factor for moyamoya disease, an inheritable idiopathic cerebrovascular disorder with arterial stenosis and occlusion at a limited site in the brain. Although the pathologic mechanism has remained largely unclear, a leading hypothesis is that mysterin plays a role in the blood vessel and that the R4810K mutation interferes with the vascular function of mysterin, resulting in the development of moyamoya disease. The first evidence that mysterin participates in normal vascular structure and/or function was obtained from zebrafish, a powerful model vertebrate. In this chapter, we overview the vascular and other phenotypes of mysterin knockdown/knockout zebrafish and discuss its possible roles in vivo.