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via intratesticular injection of peptide corresponding to a segment of the
second extracellular loop of occludin, the BTB was compromised, leading
to germ cell loss from the epithelium (
Chung et al., 2001
). Interestingly,
when occludin was deleted, occludin knockout mice remained fertile by age
6 weeks at the time the first wave of spermatogenesis occurred (
Saitou et al.,
2000
). However, these occludin knockout mice were found to be infertile
by ∼40-60 weeks of age, with their seminiferous tubules displayed atrophy
and devoid of germ cells (
Saitou et al., 2000
). Subsequent studies by generat-
ing another genetic model of occludin knockdown confirmed that fertility
was retained in these mice only from ∼6-10 weeks of age (
Takehashi et al.,
2007
), but all occludin knockout mice were infertile by 36-60 weeks of
age with the tubules devoid of spermatocytes and spermatids (
Saitou et al.,
2000
;
Takehashi et al., 2007
). Collectively, these findings illustrate that while
other TJ proteins, such as claudins and JAMs, may be able to supersede the
loss of occludin at the BTB to maintain spermatogenesis; however, occludin
is absolutely essential to maintain the BTB function and spermatogenesis
beyond 10 weeks of age in rodents during adulthood, illustrating the func-
tional relationship between BTB and maintenance of spermatogenesis.
Interestingly, the necessity of occludin to spermatogenesis does not apply
to humans as occludin was not found in human Sertoli cells in an earlier
study (
Moroi et al., 1998
). However, a recent study by RT-PCR has identified
occludin in human Sertoli cells (Xiao and Cheng, unpublished observations),
illustrating further study on the function of occludin in huamn BTB is war-
ranted. The lack of occludin in human seminiferous epithelium also illustrates
that the BTB is a complex ultrastructure and its constituency is species-spe-
cific. Other studies have also shown that the role of occludin in blood-tissue
barriers is organ- and/or tissue-specific. For instance, occludin is not essential
for the formation of TJ strands; and in some cell types, it is not even needed
for the maintenance of TJs. It was reported that occludin was not found in
the TJ strands between porcine aortic endothelial cells (
Hirase et al., 1997
),
revealing that in some tissues, occludin is not a constituent protein of the TJ
barrier. Moreover, in occludin knockout mice, the TJ barrier formed between
intestinal epithelial cells was indistinguishable from those of the wild type
ultrastructurally (
Saitou et al., 2000
), demonstrating that in some epithelia that
normally express occludin, a missing of occludin does not necessarily affect the
formation and/or maintenance of the TJ barrier. Furthermore, although stud-
ies have shown that treatment of synthetic occludin peptide disrupted TJ bar-
rier between Sertoli cells (
Chung et al., 2001
) as well as that between intestinal
epithelial cells (
Nusrat et al., 2005
), a study in human intestinal T84 epithelial
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