Claudin 11 deficiency in mice results in loss of the Sertoli cell epithelial phenotype in the testis.
Tissue integrity relies on barriers formed between epithelial cells. In the testis, the barrier is formed at the initiation of puberty by a tight junction complex between adjacent Sertoli cells, thereby defining an adluminal compartment where meiosis and spermiogenesis occur. Claudin 11 is an obligatory protein for tight junction formation and barrier integrity in the testis. It is expressed by Sertoli cells, and spermatogenesis does not proceed beyond meiosis in its absence, resulting in male sterility. Sertoli cell maturation--arrest of proliferation and expression of proteins to support germ cell development--parallels tight junction assembly; however, the pathophysiology underlying the loss of tight junctions in the mature testis remains largely undefined. Here, using immunohistochemistry and microarrays we demonstrate that adult Cldn11(-/-) mouse Sertoli cells can proliferate while maintaining expression of mature markers. Sertoli cells detach from the basement membrane, acquire a fibroblast cell shape, are eliminated through the lumen together with apoptotic germ cells, and are found in epididymis. These changes are associated with tight junction regulation as well as actin-related and cell cycle gene expression. Thus, Cldn11(-/-) Sertoli cells exhibit a unique phenotype whereby loss of tight junction integrity results in loss of the epithelial phenotype.
Mazaud-Guittot
S
S
INSERM, U870, Oullins, France.
Meugnier
E
E
Pesenti
S
S
Wu
X
X
Vidal
H
H
Gow
A
A
Le Magueresse-Battistoni
B
B
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001814:Blood-Testis Barrier; D002455:Cell Division; D016764:Cell Polarity; D054338:Cell Transdifferentiation; D057167:Claudins; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology*; D013091:Spermatogenesis; D019108:Tight Junctions / Q000502:physiology
D000199:Actins; D057167:Claudins; C492354:Cldn11 protein, mouse; D009419:Nerve Tissue Proteins