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Publication : Zona occludens-2 is critical for blood-testis barrier integrity and male fertility.

First Author  Xu J Year  2009
Journal  Mol Biol Cell Volume  20
Issue  20 Pages  4268-77
PubMed ID  19692573 Mgi Jnum  J:157381
Mgi Id  MGI:4430738 Doi  10.1091/mbc.E08-12-1236
Citation  Xu J, et al. (2009) Zona occludens-2 is critical for blood-testis barrier integrity and male fertility. Mol Biol Cell 20(20):4268-77
abstractText  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 chimera 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.
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