Disrupted compaction of CNS myelin in an OSP/Claudin-11 and PLP/DM20 double knockout mouse.

OSP/claudin-11 and PLP are both tetraspan proteins concentrated in CNS myelin. It has been proposed that they have a structural role in myelin formation and maintenance due to their localization and concentration in membrane sheaths. This hypothesis is not supported by the fact that both OSP/claudin-11- and PLP-null mice have relatively normal-appearing myelin and mild neurological deficits. Since both OSP/claudin-11 and PLP are abundant in myelin and have similar structures, the mild phenotypes of the knockout mice are likely due to compensatory mechanisms. Here we show that when both OSP/claudin-11 and PLP genes are knocked out, mice had severe neurological deficits, markedly abnormal myelin compaction, and smaller axon diameters. Interestingly, when either of these genes was knocked out, the expression of the other protein was increased. These data demonstrate that OSP/claudin-11 and PLP have essential structural functions in maintaining normal compact myelin and there is redundancy in their functions.