Failure of spermatogenesis in mouse lines deficient in the Na+-K+-2Cl(-) cotransporter

The Na+-K+-2Cl(-) cotransporter (NKCC1) carries 1 molecule of Na+ and K alo ng with 2 molecules of Cl- across the cell membrane. It is expressed in a b road spectrum of tissues and has been implicated in cell volume regulation and in ion transport by secretory epithelial tissue. However, the specific contribution of NKCC1 to the physiology of the various organ systems is lar gely undefined. We have generated mouse lines carrying either of 2 mutant a lleles of the Slc12a2 gene, which encodes this cotransporter: a null allele and a mutation that results in deletion of 72 amino acids of the cytoplasm ic domain. Both NKCC1-deficient mouse lines show behavioral abnormalities c haracteristic of mice with inner ear defects. Male NKCC1-deficient mice are infertile because of defective spermatogenesis, as shown by the absence of spermatozoa in histological sections of their epididymides and the small n umber of spermatids in their testes. Consistent with this observation, we s how that Slc12a2 is expressed in Sertoli cells, pachytene spermatocytes, an d round spermatids isolated from wild-type animals. Our results indicate a critical role for NKCC1-mediated ion transport in spermatogenesis and sugge st that the cytoplasmic domain of NKCC1 is essential in the normal function ing of this protein.