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  current news   Press   selected story    
     
  19th October 2009  
 

Zona Occludens-2 Is Critical for Blood-Testis Barrier Integrity and Male Fertility

 
 




Author
Xu J, Anuar F, Mohamed Ali S, Ng MY, Phua DC, Hunziker W.

Abstract
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 proteins ZO-1, ZO-2 and ZO-3. All three ZO-proteins have recently been inactivated in mice. While 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-/- 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.

 
 

 
 


Figure Legend: Localization of Cldn11 in testis from ZO-2 chimera. (A-I) Immunohistochemical analysis. Sections of testes from WT controls (A-F) or ZO-2 chimera (G-I) were labeled with antibodies to ZO-2 (A-C, red) or ZO-1 (D-I, red) and Cldn11 (green). DAPI (blue) was used to stain nuclei. Note that Cldn11 still extensively colocalizes with ZO-1 to the region of the BTB in ZO-2 chimera. C, F, and I show merged images. Areas where the Cldn11 labeling is delocalized and extends into the adluminal region are indicated (I, arrows). (J) Quantification. Fifty randomly chosen WT or chimera tubules were analyzed for the presence of delocalized Cldn11 labeling as shown in panel I. In >60% of the chimera tubules, the Cdln11 labeling extended into the adluminal domain.

Published: Mol Biol Cell. 2009 Sep 9. [Epub ahead of print]

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