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携带Ifitm/Fragilis基因家族簇缺失的小鼠中正常生殖系的建立。

Normal germ line establishment in mice carrying a deletion of the Ifitm/Fragilis gene family cluster.

作者信息

Lange Ulrike C, Adams David J, Lee Caroline, Barton Sheila, Schneider Robert, Bradley Allan, Surani M Azim

机构信息

Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer & Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.

出版信息

Mol Cell Biol. 2008 Aug;28(15):4688-96. doi: 10.1128/MCB.00272-08. Epub 2008 May 27.

Abstract

The family of interferon-inducible transmembrane proteins (Ifitm) consists of five highly sequence-related cell surface proteins, which are implicated in diverse cellular processes. Ifitm genes are conserved, widely expressed, and characteristically found in genomic clusters, such as the 67-kb Ifitm family locus on mouse chromosome 7. Recently, Ifitm1 and Ifitm3 have been suggested to mediate migration of early primordial germ cells (PGCs), a process that is little understood. To investigate Ifitm function during germ cell development, we used targeted chromosome engineering to generate mutants which either lack the entire Ifitm locus or carry a disrupted Ifitm3 gene only. Here we show that the mutations have no detectable effects on development of the germ line or on the generation of live young. Hence, contrary to previous reports, Ifitm genes are not essential for PGC migration. The Ifitm family is a striking example of a conserved gene cluster which appears to be functionally redundant during development.

摘要

干扰素诱导跨膜蛋白(Ifitm)家族由五个高度序列相关的细胞表面蛋白组成,这些蛋白参与多种细胞过程。Ifitm基因保守、广泛表达,且典型地存在于基因组簇中,如小鼠7号染色体上67kb的Ifitm家族基因座。最近,有人提出Ifitm1和Ifitm3介导早期原始生殖细胞(PGC)的迁移,而这一过程目前了解甚少。为了研究Ifitm在生殖细胞发育过程中的功能,我们利用靶向染色体工程技术构建了突变体,这些突变体要么缺失整个Ifitm基因座,要么仅携带一个被破坏的Ifitm3基因。在此我们表明,这些突变对生殖系的发育或活仔鼠的产生没有可检测到的影响。因此,与之前的报道相反,Ifitm基因对于PGC迁移并非必不可少。Ifitm家族是一个保守基因簇的显著例子,该基因簇在发育过程中似乎功能冗余。

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