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 reproductive deficits: CNS nerve conduction is slowed, hindlimb weakness is conspicuous, and males are sterile. Freeze fracture reveals that tight junction intramembranous strands are absent in CNS myelin and between Sertoli cells of mutant mice. Our results demonstrate that OSP is the mediator of parallel-array tight junction strands and distinguishes this protein from other intrinsic membrane proteins in tight junctions. These novel results provide direct evidence of the pivotal role of the claudin family in generating the paracellular physical barrier of tight junctions necessary for spermatogenesis and normal CNS function.
Gow
A
A
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Southwood
C M
CM
Li
J S
JS
Pariali
M
M
Riordan
G P
GP
Brodie
S E
SE
Danias
J
J
Bronstein
J M
JM
Kachar
B
B
Lazzarini
R A
RA
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D057167:Claudins; D005614:Freeze Fracturing; D018507:Gene Expression Regulation, Developmental; D000882:Haplorhini; D006614:Hindlimb / Q000254:growth & development; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats; D012708:Sertoli Cells / Q000378:metabolism* / Q000648:ultrastructure; D013737:Testis / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure
D057167:Claudins; C492354:Cldn11 protein, mouse; C492353:Cldn11 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins