CRSPR II Supplement: Consortium for the production and cryopreservation of knockout mice

参考人类基因组的注释已经鉴定了大约20，000个蛋白质编码基因， 以及3,000个非编码RNA。这些基因共同协调了有机体的发育， 支持细胞、组织、器官系统以及生理和行为的所有方面的功能。的 1000基因组计划揭示了人类基因组的非凡多样性水平，但对于大多数基因来说， 正常形式的功能和功能丧失变体的疾病后果均未知。 小鼠为理解基因及其变体的功能提供了一条途径。IVIice股份 发育、生理、解剖和代谢与人类相似，这在健康的 以及疾病状态。这反映了两个物种基因的相似性。产生的突变小鼠 使用ES细胞技术是一种灵敏的生物测定系统， 功能，并为进一步研究提供了持久的生物资源。 该建议的目的是从条件性ES细胞资源中产生突变小鼠， 在先前NIH（KOMP）和EU（EUCOMM）资助的项目下产生的靶向lacZ标记等位基因。 我们和其他人将用这些老鼠来发现基因的功能。我们建议执行这项工作（^ 并形成了一个由三个研究所（贝勒医学院、桑格研究所）组成的联合体 和MRC Harwell）作为平等伙伴共同努力实现这一目标。我们将培育出老鼠 对应于由桑格研究所分发的来自ES细胞的1500个突变基因。我们将描述 每个靶基因的成体和胚胎表达模式以及育种决定了 胚胎发育和生育力的每一个要求，如果有的话。所有的等位基因都会被冷冻保存 并放置在存储库中，所有数据将存放在集中的数据协调中心， 支持进一步研究。 相关性（参见说明）： 在一个典型的人身上，20,000个基因中的大多数都是正常的，但我们也有几百个基因被破坏了。 虽然一些断裂的基因可以导致严重的疾病，如囊性纤维化或癌症，其他人几乎没有或 没有后果，或者只有在压力下才能发挥作用。目前，我们已经了解了 只有人类基因的三分之一。如果我们要充分了解人类健康和疾病， 基因功能的知识。

Annotation of the reference human genome has identified approximately 20,000 protein coding genes as well as 3,000 non-coding RNAs. Together these genes orchestrate the development of the organism, supporting all aspects of the function of cells, tissues, organ systems as well physiology and behavior. The lOOOgenome project has revealed extraordinary levels of diversity in human genomes, yet for most genes neither the function of normal version nor the disease consequence of loss-of-function variants is known. The mouse provides a route to understand the function of genes and their variants. IVIice share developmental, physiological, anatomical and metabolic parallels with humans, which are evident in healthy as well as diseased states. These reflect similarities of the genes in both species. Mutant mice generated using ES cell technology are a sensitive biological assay system from which a deep understanding of function can be gleaned and they also provide a long lasting biological resource for further study. The objective of this proposal is to generate mutant mice from a resource of ES cells with conditionally targeted, lacZ-tagged alleles generated under previous NIH (KOMP) and EU (EUCOMM) funded programs. We and others will use these mice to discover the function of genes. We are proposing to carry out this wor(^ at scale and have formed a consortium of three Institutes (Baylor College of Medicine, the Sanger Institute and MRC Harwell) to work together as equal partners to achieve this objective. We will generate mice corresponding to 1500 mutant genes from ES cells distributed by the Sanger Institute. We will characterize the adult and embryonic expression pattern of the each targeted gene and by breeding determine the requirement of each for embryonic development and fertility, if any. All of the alleles will be cryo-preserved and placed in a repository and all of the data will be deposited in a centralized data coordination center to support further studies. RELEVANCE (See instructions): Most of the 20,000 genes in a typical person are normal but we also have several hundred broken ones. While some broken genes can cause severe disease such as cystic fibrosis or cancer, others have little or no consequence, or function only under stress. Currently we have some understanding of the function of just one third of human genes. If we are to fully understand human health and disease we must expand knowledge of gene function to all of our genes.