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

Laminin 1 Chain Corrects Male Infertility Caused by Absence of Laminin 2 Chain

Mattias Häger^*, Kinga Gawlik^*, Alexander Nyström^*, Takako Sasaki 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, Martinsried, Germany

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

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