Department of Anatomy and Developmental Biology, The Australian Research Council (ARC), Centre of Excellence in Biotechnology and Development, Monash University, Melbourne, Victoria 3800, Australia.
Asian J Androl. 2011 Jan;13(1):139-51. doi: 10.1038/aja.2010.101. Epub 2010 Nov 8.
Limited knowledge of the genetic causes of male infertility has resulted in few treatment and targeted therapeutic options. Although the ideal approach to identify infertility causing mutations is to conduct studies in the human population, this approach has progressed slowly due to the limitations described herein. Given the complexity of male fertility, the entire process cannot be modeled in vitro. As such, animal models, in particular mouse models, provide a valuable alternative for gene identification and experimentation. Since the introduction of molecular biology and recent advances in animal model production, there has been a substantial acceleration in the identification and characterization of genes associated with many diseases, including infertility. Three major types of mouse models are commonly used in biomedical research, including knockout/knockin/gene-trapped, transgenic and chemical-induced point mutant mice. Using these mouse models, over 400 genes essential for male fertility have been revealed. It has, however, been estimated that thousands of genes are involved in the regulation of the complex process of male fertility, as many such genes remain to be characterized. The current review is by no means a comprehensive list of these mouse models, rather it contains examples of how mouse models have advanced our knowledge of post-natal germ cell development and male fertility regulation.
男性不育的遗传原因知之甚少,导致治疗和靶向治疗选择有限。尽管识别导致不育的突变的理想方法是在人群中进行研究,但由于本文所述的限制,这一方法进展缓慢。鉴于男性生育能力的复杂性,整个过程无法在体外进行建模。因此,动物模型,特别是小鼠模型,为基因鉴定和实验提供了有价值的替代方法。自从分子生物学的引入和动物模型生产的最新进展以来,与许多疾病(包括不育症)相关的基因的鉴定和特征描述已经大大加速。在生物医学研究中,通常使用三种主要类型的小鼠模型,包括基因敲除/敲入/基因捕获、转基因和化学诱导点突变小鼠。使用这些小鼠模型,已经揭示了 400 多个对男性生育力至关重要的基因。然而,据估计,有数千个基因参与调节男性生育力这一复杂过程,因为还有许多这样的基因有待鉴定。本综述绝不是这些小鼠模型的全面清单,而是包含了小鼠模型如何推进我们对出生后生殖细胞发育和男性生育力调节的认识的例子。