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Sci Rep. 2018 Jul 10;8(1):10379. doi: 10.1038/s41598-018-28666-6.

AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice.

Author information

1
Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
2
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
3
Genetic Epigenetic and Therapies of Infertility, Institute for Advanced Biosciences, Inserm U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, F-38000, France.
4
UM GI-DPI, CHU Grenoble Alpes, Grenoble, F-38000, France.
5
Office of the President, Ballou Hall, Tufts University, Medford, MA, 02155, USA.
6
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK. Zoltan.Molnar@dpag.ox.ac.uk.
7
Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. avelayos@well.ox.ac.uk.
8
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK. avelayos@well.ox.ac.uk.

Abstract

Study of knockout (KO) mice has helped understand the link between many genes/proteins and human diseases. Identification of infertile KO mice provides valuable tools to characterize the molecular mechanisms underlying gamete formation. The KIAA0319L gene has been described to have a putative association with dyslexia; surprisingly, we observed that homozygous KO males for AU040320, KIAA0319L ortholog, are infertile and present a globozoospermia-like phenotype. Mutant spermatozoa are mostly immotile and display a malformed roundish head with no acrosome. In round spermatids, proacrosomal vesicles accumulate close to the acroplaxome but fail to coalesce into a single acrosomal vesicle. In wild-type mice AU040320 localises to the trans-Golgi-Network of germ cells but cannot be detected in mature acrosomes. Our results suggest AU040320 may be necessary for the normal formation of proacrosomal vesicles or the recruitment of cargo proteins required for downstream events leading to acrosomal fusion. Mutations in KIAA0319L could lead to human infertility; we screened for KIAA0319L mutations in a selected cohort of globozoospermia patients in which no genetic abnormalities have been previously identified, but detected no pathogenic changes in this particular cohort.

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