Deletion of repetitive gene families

随着人类和小鼠基因组的完成测序，大量的基因被发现。这些基因中的许多被发现在染色体上聚集在一起，并且高度相关。目前研究小鼠单个基因的技术不足以研究高度重复和相关的基因家族的作用。在小鼠胚胎干细胞中进行染色体工程提供了一种方法，可以删除这些大的基因家族，然后产生基因家族缺陷的小鼠，可以用来研究这些基因在人类中的可能作用。小鼠6号染色体上的自然杀伤基因复合体是完善小鼠ES细胞染色体缺失的完美遗传游乐场。NKC是几个不同基因家族(Ly49、Nkrp1、Nkg2)的发源地，这些基因家族控制着自然杀伤细胞的功能，自然杀伤细胞是一种抗击病毒感染和癌症的白细胞。我们计划利用这些NKC基因家族来优化现有的缺失技术。这方面的成功将使多个研究领域受益，包括免疫学(NKC、干扰素)、发育生物学(Hox)和神经科学(嗅觉)，这些领域中的每一个都有重复的基因家族模型，需要仔细检查，但缺乏适当的技术工具。

With the complete sequencing of the human and mouse genomes a large number of genes have been discovered. Many of these genes are found grouped together on chromosomes and are highly related. Current technology for studying individual genes in mice is not adequate to study the role of highly repetitive and related gene families. The engineering of chromosomes in mouse embryonic stem cells offers a way to delete these large gene families and to then produce a gene family-deficient mouse, which can be used to study the possible role of these genes in humans. The natural killer gene complex on mouse chromosome 6 is a perfect genetic playground to perfect chromosome deletion in mouse ES cells. The NKC is the home of several different gene families (Ly49, Nkrp1, Nkg2) that govern the function of natural killer cells, a type of white blood cell that fights viral infections and cancers. We plan to optimize the available deletion technology using these NKC gene families. Success here will benefit several fields of research including immunology (NKC, IFN), developmental biology (Hox), and neuroscience (olfaction), each of which has repetitive gene family models that require scrutiny, but lack proper technological tools.