Failure of spermatogenesis in mouse lines deficient in the Na+-K+-2Cl– cotransporter
Amy J. Pace, … , Deborah A. O’Brien, Beverly H. Koller
Amy J. Pace, … , Deborah A. O’Brien, Beverly H. Koller
Published February 15, 2000
Citation Information: J Clin Invest. 2000;105(4):441-450. https://doi.org/10.1172/JCI8553.
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Article

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

Abstract

The Na+-K+-2Cl– cotransporter (NKCC1) carries 1 molecule of Na+ and K+ along with 2 molecules of Cl– across the cell membrane. It is expressed in a broad 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 largely undefined. We have generated mouse lines carrying either of 2 mutant alleles of the Slc12a2 gene, which encodes this cotransporter: a null allele and a mutation that results in deletion of 72 amino acids of the cytoplasmic domain. Both NKCC1-deficient mouse lines show behavioral abnormalities characteristic 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 number of spermatids in their testes. Consistent with this observation, we show that Slc12a2 is expressed in Sertoli cells, pachytene spermatocytes, and round spermatids isolated from wild-type animals. Our results indicate a critical role for NKCC1-mediated ion transport in spermatogenesis and suggest that the cytoplasmic domain of NKCC1 is essential in the normal functioning of this protein.

Authors

Amy J. Pace, Eddie Lee, Krairek Athirakul, Thomas M. Coffman, Deborah A. O’Brien, Beverly H. Koller

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Northern analysis of NKCC1 expression in the testes of maturing animals ...
Northern analysis of NKCC1 expression in the testes of maturing animals and in specific testis cell populations. A normal 6.5-kb NKCC1 transcript is observed in the testis throughout postnatal development. The presence of an alternate transcript is detected in 7- and 14-day-old mice, and this 4.2-kb transcript becomes more abundant in 21-day-old mice. This alternate transcript is also detected in pachytene spermatocytes and round spermatids in addition to the normal NKCC1 transcript, whereas only the 6.5-kb transcript is detected in Sertoli cells. RNA loading is 20 μg for the testis samples and 10 μg for the isolated cell types. Analysis of 18S RNA is shown to demonstrate equal loading of the samples.