CNS myelin and Sertoli cell tight junction strands are absent in Osp/Claudin-11 null mice

Oligodendrocyte-specific protein (OSP)/claudin-11 is a recently identified transmembrane protein found in CNS myelin and testis with unknown function. Herein we demonstrate that Osp null mice exhibit both neurological and rep roductive deficits: CNS nerve conduction is slowed, hindlimb weakness is co nspicuous, and males are sterile. Freeze fracture reveals that tight juncti on intramembranous strands are absent in CNS myelin and between Sertoli cel ls of mutant mice. Our results demonstrate that OSP is the mediator of para llel-array tight junction strands and distinguishes this protein from other intrinsic membrane proteins in tight junctions. These novel results provid e direct evidence of the pivotal role of the claudin family in generating t he paracellular physical barrier of tight junctions necessary for spermatog enesis and normal CNS function.