Zona occludens-2 is critical for blood-testis barrier integrity and male fertility.
Tight junction integral membrane proteins such as claudins and occludin are tethered to the actin cytoskeleton by adaptor proteins, notably the closely related zonula occludens (ZO) proteins ZO-1, ZO-2, and ZO-3. All three ZO proteins have recently been inactivated in mice. Although ZO-3 knockout mice lack an obvious phenotype, animals deficient in ZO-1 or ZO-2 show early embryonic lethality. Here, we rescue the embryonic lethality of ZO-2 knockout mice by injecting ZO-2(-/-) embryonic stem (ES) cells into wild-type blastocysts to generate viable ZO-2 chimera. ZO-2(-/-) ES cells contribute extensively to different tissues of the chimera, consistent with an extraembryonic requirement for ZO-2 rather than a critical role in epiblast development. Adult chimera present a set of phenotypes in different organs. In particular, male ZO-2 chimeras show reduced fertility and pathological changes in the testis. Lanthanum tracer experiments show a compromised blood-testis barrier. Expression levels of ZO-1, ZO-3, claudin-11, and occludin are not apparently affected. ZO-1 and occludin still localize to the blood-testis barrier region, but claudin-11 is less well restricted and the localization of connexin-43 is perturbed. The critical role of ZO-2 for male fertility and blood-testis barrier integrity thus provides a first example for a nonredundant role of an individual ZO protein in adult mice.
Xu
Jianliang
J
Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
Anuar
Farhana
F
Ali
Safiah Mohamed
SM
Ng
Mei Yong
MY
Phua
Dominic C Y
DC
Hunziker
Walter
W
D000818:Animals; D001814:Blood-Testis Barrier / Q000502:physiology*; D002678:Chimera; D057167:Claudins; D018031:Connexin 43 / Q000032:analysis; D005260:Female; D055786:Gene Knockout Techniques; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D007811:Lanthanum / Q000493:pharmacokinetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000032:analysis; D062793:Occludin; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D012708:Sertoli Cells / Q000737:chemistry / Q000473:pathology*; D019108:Tight Junctions / Q000737:chemistry / Q000473:pathology*; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
D057167:Claudins; C492354:Cldn11 protein, mouse; D018031:Connexin 43; C543076:GJA1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; C569047:Tjp2 protein, mouse; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; C016534:lanthanide nitrate; D007811:Lanthanum
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