Fig. 2.

Published NOX4 knock-out (KO) mouse models. a Wild-type NOX4 has six transmembrane helices and cytosolic binding domains for FAD and NADPH at the C-terminus. b Deletion of exons 1 and 2 should delete the complete NOX4 protein [32]. c Deletion of exon 4 only leaves the first transmembrane domain of NOX4. However, hypothetically, this may also result in the formation of a splice variant that contains both FAD and NADPH binding domains and thus has remaining ROS-forming activity [43]. d Another knock-out was generated by conditionally deleting exon 9 of NOX4 in cardiomyocytes, thereby deleting the FAD binding domain, likely leaving a non-functional enzyme [34]. e The fourth published NOX4 KO mouse was generated by deleting exons 14 and 15 that refer to the NADPH binding domain. This likely results in the expression of a non-functional enzyme [33]