Human Molecular Genetics Advance Access published online on May 20, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm117
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The Testis Anion Transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse
1 Institut Cochin, Université Paris Descartes, CNRS (UMR8104), Paris, France 2 INSERM, U567, Paris, France 3a Target Discovery Department. N.V. Organon. P.O. Box 20-5340 BH. Oss, The Netherlands 3b Molecular Pharmacology Department. N.V. Organon. P.O. Box 20-5340 BH. Oss, The Netherlands 4 GERHM, IFR 140. Université de Rennes I. Rennes, France 5 INSERM, U625, Rennes, France 6 Université Paris XI, Département d'Andrologie, Le Kremlin-Bicêtre, France
* Correspondence: Gérard Gacon, Institut Cochin, Département Génétique et Développement, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France. Tel: +33.(0)1.44.41.24.70, Fax: +33.(0)1.44.41.24.21, E-mail: gacon{at}cochin.inserm.fr
Received November 14, 2006; Revised April 27, 2007; Accepted April 27, 2007
The Slc26 family is a conserved family of anion transporters. In the human, their physiological relevance was highlighted with the discovery of pathogenic mutations in several Slc26 transporters that lead to distinctive clinical disorders (Pendred syndrome, deafness, diastrophic dysplasia, congenital chloride diarrhoea) that are related to the specific distribution of these genes.
We previously identified TAT1 as a new family member (Slc26A8), very specifically expressed in male germ cells in both the human and the mouse. To investigate Tat1 function in the male germline, we generated mice with a targeted disruption of the Tat1 gene. Heterozygous and homozygous Tat1 mutant mice were indistinguishable from wild-type littermates concerning survival rate, general appearance and gross behaviour; however, Tat1 null males were sterile due to complete lack of sperm motility and reduced sperm fertilization potential. Ultra-structural analysis revealed defects in flagellar differentiation leading to an abnormal annulus, disorganization of the midpiece-principal piece junction, hairpin bending of the sperm tail with disruption of the axial structures, and abnormal mitochondrial sheath assembly. While ATP levels were normal, ATP consumption was strongly reduced in Tat1 null spermatozoa. Interestingly, Tat1 is located at the annulus, a septin-based circular structure connecting the midpiece to the principal piece. Altogether, our results indicate that Tat1 is a critical component of the sperm annulus that is essential for proper sperm tail differentiation and motility.
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