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

The functions of some CLC Cl- channels are evident from human diseases that result from their mutations, but the rule of the broadly expressed CIC-2 C l- channel is less clear. Several important functions have been attributed to CIC-2, but contrary to these expectations CIC-2-deficient mice lacked ov ert abnormalities except for a severe degeneration of the retina and the te stes, 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 no rmally express CIC-2 in patches adjacent to germ cells. In the retina, phot oreceptors lacked normal outer segments and degenerated between days P10 an d P30. The current across the retinal pigment epithelium was severely reduc ed at P36, Thus, CIC-2 disruption entails the death of two cell types which depend on supporting cells that form the blood-testes and blood-retina bar riers. We propose that CIC-2 is crucial for controlling the ionic environme nt of these cells.