Mouse Core

我们最初设计鼠标内核的目的是创造一个与其他鼠标内核截然不同的内核。我们的首要目标是使用小鼠核心产生新的转基因和基因靶向小鼠品系，使我们能够作为一个群体进行测试， 内耳生物学的基本问题。因此，我们预期小鼠核心在构建体设计和生成、小鼠饲养和基因分型方面具有专业知识。 第一次更新提交的评审员很容易就发现了一个不可否认的事实，即我们在制作新的鼠标线方面远没有我们所熟悉的那么成功。我们最初的意图是通过生成小鼠品系来为构建体生成过程提供种子 这与核心PI的利益更密切相关，但仍然涉及OHRC小组普遍感兴趣的主题，如机械转导。 然而，小鼠核心陷入了构建体生成和获得生殖系的困境， 传输及其结构。我们现在可以开始在小组中分享两个产生的小鼠品系（TRPV 5和TRPV 6敲入），但我们更希望几年前就在这里。 此外，老鼠核心科学家吉姆·斯马特（Jim Smart）有能力管理核心的各个方面，他去了一个更稳定的职位，一个有长期就业保证的职位。我们很幸运，以我们付给他的薪水找到了他，因为他很有经验;我们 他刚从研究生院毕业就被选中了，并且能够给他足够的补偿，使这个职位看起来很有吸引力。然而，这不是这一立场的长期解决办法。这一经验确实指出，雇用有经验的人， 鼠标线是不容易做到与现有的P30预算。 然而，在此期间，我们聘请了一位鼠标核心技术人员Michael Bateschell，他在核心的面向服务方面表现出了出色的技能。结合保留Bateschell的需要和扩大核心以包括子宫内电穿孔的计划，很明显，我们无法为核心雇用具有足够分子遗传学经验的人，以便能够继续构建一代 的服务.该核心在其第一次更新提交后的负面审查只是加强了这一观点。

Our original intent with the Mouse Core was to create a core that was rather different than other mouse cores. Our overarching goal was to use the Mouse Core to generate new transgenic and gene-targeted mouse lines that would allow us to test, as a group, fundamental problems in inner-ear biology. We intended therefore for the Mouse Core to have experfise in construct design and generafion, mouse husbandry, and genotyping. The reviewers of the first renewal submission easily picked up on the undeniable fact that we were far less successful than we had anficipated in making new mouse lines. Our original intent was to seed the construct-generation process by generating mouse lines that were more closely related to the interests of the Core PI, but that nevertheless tapped into topics of general interest to the OHRC group, such as mechanotransduction. However, the Mouse Core bogged down with construct generation and in obtaining germline transmission with its constructs. We are now at a position where we can begin to share the two generated mouse lines (TRPV5 and TRPV6 knock-ins) amongst the group, but we would have preferred to be here a few years ago. Moreover, the Mouse Core Scienfist, Jim Smart, who was capable of running all facets of the core, left for a more stable posifion, one with a long-term guarantee of employment. We had been lucky to get him at the salary we paid him, as he was quite experienced; we picked him straight out of graduate school, and were able to give him sufficient compensafion for the position to look attractive. That was not a long-term solufion for this position, however. This experience did point out that hiring someone with experience in making mouse lines was not easily done with the available P30 budget. In the meanfime, however, we had hired a Mouse Core Technician, Michael Bateschell, who demonstrated outstanding skill in the service-oriented aspects of the core. Combining the need to retain Bateschell and the plan to expand the core to included in utero electroporation, it became abundantly clear that we would not be able to hire someone for the core with sufficient molecular-genetics experience to be able to continue with the construct-generation service. The negative review of this core after its first renewal submission just reinforced this view.