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  • The EMBO Journal (2001) 20, 1289 - 1299
  • doi:10.1093/emboj/20.6.1289

Male germ cells and photoreceptors, both dependent on close cell–cell interactions, degenerate upon ClC-2 Cl- channel disruption

Michael R. Bösl1,5, Valentin Stein1,5, Christian Hübner1, Anselm A. Zdebik1,2, Sven-Eric Jordt1,2, Amal K. Mukhopadhyay3, Michail S. Davidoff4, Adolf-Friedrich Holstein4 and Thomas J. Jentsch1

  1. Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), Martinistras zlige 52, D-20246 Hamburg, Germany
  2. Present address: Department of Cellular and Molecular Pharmacology, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0450, USA
  3. Institut für Hormon- und Fortpflanzungsforschung (IHF), Grandweg 64, D-22529 Hamburg, Germany
  4. Institut für Anatomie, Universität Hamburg, Martinistras zlige 52, D-20246 Hamburg, Germany
  5. M.R.Bösl and V.Stein contributed equally to this work

Correspondence to:

Thomas J. Jentsch, E-mail: jentsch@zmnh.uni-hamburg.de

Received 30 October 2000; Accepted 26 January 2001; Revised 26 January 2001

The functions of some CLC Cl- channels are evident from human diseases that result from their mutations, but the role of the broadly expressed ClC-2 Cl- channel is less clear. Several important functions have been attributed to ClC-2, but contrary to these expectations ClC-2-deficient mice lacked overt abnormalities except for a severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina and germ cells failed to complete meiosis. Beginning around puberty there was a massive death of primary spermatocytes and later also of spermatogonia. Tubules were filled with abnormal Sertoli cells, which normally express ClC-2 in patches adjacent to germ cells. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, ClC-2 disruption entails the death of two cell types which depend on supporting cells that form the blood–testes and blood–retina barriers. We propose that ClC-2 is crucial for controlling the ionic environment of these cells.

  • Keywords:

    • anion channel,
    • epilepsy,
    • knock-out,
    • retinal degeneration,
    • Sertoli cell only syndrome