Fidgetin-Like1 Is a Strong Candidate for a Dynamic Impairment of Male Meiosis Leading to Reduced Testis Weight in Mice
2011
L'Hôte , David (Centre National de la Recherche ScientifiqueUniversité Paris 7, ParisParis(France). UMR 7592, Institut Jacques Monod, Equipe Génétique et Génomique du Développement Gonadique) | Vatin , Magalie ( Institut National de la Santé et de la Recherche MédicaleUniversité Paris Descartes (Paris 5), Paris Paris(France). U1016 Département de Génétique et Développement, Institut Cochin) | Auer , Jana ( Institut National de la Santé et de la Recherche MédicaleUniversité Paris Descartes (Paris 5), Paris Paris(France). U1016 Département de Génétique et Développement, Institut Cochin) | Castille , Johan (INRA , Jouy-En-Josas (France). UMR 1313 Génétique Animale et Biologie Intégrative) | Passet , Bruno (INRA , Jouy-En-Josas (France). UMR 1313 Génétique Animale et Biologie Intégrative) | Montagutelli , Xavier (Institut Pasteur, Paris(France). Unité de Génétique des Mammifères) | Serres , Catherine ( Institut National de la Santé et de la Recherche MédicaleUniversité Paris Descartes (Paris 5), Paris Paris(France). U1016 Département de Génétique et Développement, Institut Cochin) | Vaiman , Daniel (auteur de correspondance) ( Institut National de la Santé et de la Recherche MédicaleUniversité Paris Descartes (Paris 5), Paris Paris(France). U1016 Département de Génétique et Développement, Institut Cochin)
Background: In a previous work, using an interspecific recombinant congenic mouse model, we reported a genomic region of 23 Mb on mouse chromosome 11 implicated in testis weight decrease and moderate teratozoospermia (~20–30%), a Quantitative Trait Locus (QTL) called Ltw1. The objective of the present study is to identify the gene underlying this phenotype.[br/] Results: In the present study, we refined the QTL position to a 5 Mb fragment encompassing only 11 genes. We showed that the low testis weight phenotype was due to kinetic alterations occurring during the first wave of the spermatogenesis where we could point out to an abnormal lengthening of spermatocyte prophase. We identify Fidgetin-like 1 (Fignl1) as the gene underlying the phenotype, since if fulfilled both the physiological and molecular characteristics required. Indeed, amongst the 11 positional candidates it is the only gene that is expressed during meiosis at the spermatocyte stage, and that presents with non-synonymous coding variations differentiating the two mouse strains at the origin of the cross.[br/] Conclusions: This work prompted us to propose Fignl1 as a novel actor in mammal's male meiosis dynamics which has fundamental interest. Besides, this gene is a new potential candidate for human infertilities caused by teratozoospermia and blockades of spermatogenesis. In addition this study demonstrates that interspecific models may be useful for understanding complex quantitative traits.
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