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用于定义精子发生过程中基因功能的果蝇工具集。

A Drosophila toolkit for defining gene function in spermatogenesis.

作者信息

Siddall N A, Hime G R

机构信息

Department of Anatomy and NeuroscienceThe University of Melbourne, Parkville, Victoria, Australia.

Department of Anatomy and NeuroscienceThe University of Melbourne, Parkville, Victoria, Australia

出版信息

Reproduction. 2017 Apr;153(4):R121-R132. doi: 10.1530/REP-16-0347. Epub 2017 Jan 10.

Abstract

Expression profiling and genomic sequencing methods enable the accumulation of vast quantities of data that relate to the expression of genes during the maturation of male germ cells from primordial germ cells to spermatozoa and potential mutations that underlie male infertility. However, the determination of gene function in specific aspects of spermatogenesis or linking abnormal gene function with infertility remain rate limiting, as even in an era of CRISPR analysis of gene function in mammalian models, this still requires considerable resources and time. Comparative developmental biology studies have shown the remarkable conservation of spermatogenic developmental processes from insects to vertebrates and provide an avenue of rapid assessment of gene function to inform the potential roles of specific genes in rodent and human spermatogenesis. The vinegar fly, Drosophila melanogaster, has been used as a model organism for developmental genetic studies for over one hundred years, and research with this organism produced seminal findings such as the association of genes with chromosomes, the chromosomal basis for sexual identity, the mutagenic properties of X-irradiation and the isolation of the first tumour suppressor mutations. Drosophila researchers have developed an impressive array of sophisticated genetic techniques for analysis of gene function and genetic interactions. This review focuses on how these techniques can be utilised to study spermatogenesis in an organism with a generation time of 9 days and the capacity to introduce multiple mutant alleles into an individual organism in a relatively short time frame.

摘要

表达谱分析和基因组测序方法能够积累大量与雄性生殖细胞从原始生殖细胞到精子成熟过程中基因表达相关的数据,以及导致男性不育的潜在突变。然而,确定特定精子发生过程中的基因功能或将异常基因功能与不育联系起来仍然是限速步骤,因为即使在哺乳动物模型中利用CRISPR进行基因功能分析的时代,这仍需要大量资源和时间。比较发育生物学研究表明,从昆虫到脊椎动物,精子发生发育过程具有显著的保守性,并提供了一种快速评估基因功能的途径,以了解特定基因在啮齿动物和人类精子发生中的潜在作用。果蝇作为发育遗传学研究的模式生物已有一百多年的历史,对该生物的研究产生了一些开创性的发现,如基因与染色体的关联、性别认同的染色体基础、X射线的诱变特性以及首个肿瘤抑制基因突变的分离。果蝇研究人员已经开发出一系列令人印象深刻的复杂遗传技术,用于分析基因功能和遗传相互作用。本综述重点关注如何利用这些技术来研究一种世代周期为9天且能够在相对较短时间内将多个突变等位基因导入单个生物体的生物的精子发生过程。

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