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(American Journal of Pathology. 2005;167:823-833.)
© 2005 American Society for Investigative Pathology

Laminin {alpha}1 Chain Corrects Male Infertility Caused by Absence of Laminin {alpha}2 Chain

Mattias Häger*, Kinga Gawlik*, Alexander Nyström*, Takako Sasaki{dagger} and Madeleine Durbeej*

From the Department of Experimental Medical Science,* Division for Cell and Matrix Biology, University of Lund, Lund, Sweden; and Max-Planck-Institut fur Biochemie,{dagger} Martinsried, Germany

Laminins are important for basement membrane structure and function. The laminin {alpha}2 chain is a major component of muscle basement membranes, and mutations in the laminin {alpha}2 gene lead to congenital muscular dystrophy in humans and mice. Although the laminin {alpha}2 chain is prominently expressed in testicular basement membranes, its role in testis has remained unclear. Here, we show that laminin {alpha}1, {alpha}2, ß1, ß2, {gamma}1, and {gamma}3 chains are the major laminin chains in basement membranes of seminiferous tubules. In laminin {alpha}2 chain-deficient dy3K/dy3K mice, lack of laminin {alpha}2 chain led to concurrent reduction of laminin {gamma}3 chain and abnormal testicular basement membranes. Seminiferous tubules of laminin {alpha}2 chain-deficient dy3K/dy3K mice displayed a defect in the timing of lumen formation, resulting in production of fewer spermatides. We also demonstrate that overexpression of laminin {alpha}1 chain in testis of dy3K/dy3K mice compensated for laminin {alpha}2 chain deficiency and significantly reversed the appearance of the histopathological features. We thus provide genetic data that laminin {alpha} chains are essential for normal testicular function in vivo.





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