L'Hôte David, Serres Catherine, Laissue Paul, Oulmouden Ahmad, Rogel-Gaillard Claire, Montagutelli Xavier, Vaiman Daniel
Equipe 21, Génomique et Epigénetique des Pathologies Placentaires, Unité INSERM 567/UMR CNRS 8104-Université Paris, Paris, France.
Genetics. 2007 Jul;176(3):1907-21. doi: 10.1534/genetics.107.072157. Epub 2007 May 4.
In mammals, male fertility is a quantitative feature determined by numerous genes. Until now, several wide chromosomal regions involved in fertility have been defined by genetic mapping approaches; unfortunately, the underlying genes are very difficult to identify. Here, 53 interspecific recombinant congenic mouse strains (IRCSs) bearing 1-2% SEG/Pas (Mus spretus) genomic fragments disseminated in a C57Bl/6J (Mus domesticus) background were used to systematically analyze male fertility parameters. One of the most prominent advantages of this model is the possibility of analyzing stable phenotypes in living animals. Here, we demonstrate the possibility in one-step fine mapping for several fertility traits. Focusing on strains harboring a unique spretus fragment, we could unambiguously localize two testis and one prostate weight-regulating QTL (Ltw1, Ltw2, and Lpw1), four QTL controlling the sperm nucleus shape (Sh1, Sh2, Sh3, and Sh4), and one QTL influencing sperm survival (Dss1). In several cases, the spretus DNA fragment was small enough to propose sound candidates. For instance, Spata1, Capza, and Tuba7 are very strong candidates for influencing the shape of the sperm head. Identifying new genes implied in mammalian fertility pathways is a necessary prerequisite for clarifying their molecular grounds and for proposing diagnostic tools for masculine infertilities.
在哺乳动物中,雄性生育能力是一个由众多基因决定的数量性状。到目前为止,通过遗传图谱方法已经确定了几个与生育能力相关的广泛染色体区域;不幸的是,其 underlying 基因很难鉴定。在这里,使用了53个种间重组近交小鼠品系(IRCSs),它们携带1-2%的SEG/Pas(小家鼠)基因组片段,散布在C57Bl/6J(家鼠)背景中,用于系统分析雄性生育参数。该模型最突出的优点之一是有可能在活体动物中分析稳定的表型。在这里,我们展示了对几个生育性状进行一步精细定位的可能性。聚焦于携带独特小家鼠片段的品系,我们能够明确地定位两个睾丸和一个前列腺重量调节QTL(Ltw1、Ltw2和Lpw1)、四个控制精子核形状的QTL(Sh1、Sh2、Sh3和Sh4)以及一个影响精子存活的QTL(Dss1)。在几种情况下,小家鼠DNA片段足够小,可以提出合理的候选基因。例如,Spata1、Capza和Tuba7是影响精子头部形状的非常有力的候选基因。鉴定哺乳动物生育途径中涉及的新基因是阐明其分子基础以及提出男性不育诊断工具的必要前提。