Journal Article

The Testis Anion Transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse

Aminata Touré, Pierre Lhuillier, Jan A. Gossen, Cor W. Kuil, David Lhôte, Bernard Jégou, Denise Escalier and Gérard Gacon

in Human Molecular Genetics

Volume 16, issue 15, pages 1783-1793
Published in print August 2007 | ISSN: 0964-6906
Published online May 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm117
The Testis Anion Transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse

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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.

Journal Article.  6821 words.  Illustrated.

Subjects: Genetics and Genomics

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