INBREEDING AND DISSEMINATION OF RETINAL MUTANT MICE

视网膜突变小鼠的近交和传播

• 批准号: 3263536
• 负责人: RICHARD L SIDMAN
• 金额: $ 15.15万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3263536
• 关键词: animal breeding; animal colony; biomedical facility; disease /disorder model; genetic disorder; genetic strain; laboratory mouse; model design /development; mutant; ophthalmoscopy; retina; retina degeneration; retina disorder; vision disorders

The aims of this grant are (1 to place mutations affecting the retina in mice onto a few selected genetic backgrounds by standard breeding schedules, so that the gene actions can be more accurately compared and contrasted with one another, 2) to distribute affected and control mice or tissues or chemical extracts to qualified research scientists at no charge to them except for shipping costs, so that they can carry on their research without committing the time or bearing the expense of generating their own mice, and 3) to mutagenize male mice and mate them with females carrying known retinal mutations, so as to select for new mutant alleles that will illuminate how particular genes control retinal function and cause disease. Progeny of mutagenized mice will be screened for retinal disease by nondestructive indirect ophthalmoscopy, a rapid and effective method that markedly reduces the need to screen laboriously by expensive histological methods.These mouse models have been adding significantly to our understanding of inherited diseases of the retinitis pigmentosa category in humans, and are likely to contribute even more crucially in the years immediately ahead. The most widely used mutations at present are named retinal degeneration (rd), retinal degeneration slow (rds), Purkinje cell degeneration (pcd), and nervous (nr). We maintain each of these on several genetic backgrounds, including three independently-occurring mutant alleles at the pcd locus. We have developed, or are developing, most of these strains, and are the unique holder of several of them. Additionally, we will supply mice with new retinal disorders named hugger (hug), vitiligo (vit), and wabbler lethal-2J (wl2J); these affect not only retinal photoreceptor cells, the hallmark of the retinitis pigmentosa class of diseases, but also affect other components of the retina, and thus open the prospect of deepening our understanding of genetic control and functions of cells in retinal pigment epithelium and inner nuclear and ganglion cell layers. Further available mutants serve as models of congenital stationary night blindness. Still others cause hypopigmentation and developmental abnormalities in the trajectories of ganglion cell axons in the optic nerve. We are prepared also to advise other investigators, as we have done during the first funding cycle of this grant, concerning what mutants, genetic backgrounds, controls, ages, and numbers of mice might help to solve their research questions. Another service function will be to take on the propagation and dissemination of mutant stocks, including transgenic mice with retinal abnormalities, that are developed by other investigators who may not wish to remain solely responsible for holding and distributing such research material.

这笔赠款的目的是（1 将影响视网膜的突变置于 通过标准育种将小鼠引入一些选定的遗传背景 时间表，以便可以更准确地比较和比较基因作用 相互对比，2) 分配受影响的小鼠和对照小鼠 或组织或化学提取物给合格的研究科学家，无需 向他们收取除运费外的费用，以便他们可以继续他们的 无需投入时间或承担生成费用的研究 他们自己的小鼠，以及3）诱变雄性小鼠并将其与雌性交配 携带已知的视网膜突变，从而选择新的突变等位基因 这将阐明特定基因如何控制视网膜功能 引起疾病。 诱变小鼠的后代将进行视网膜筛查 通过非破坏性间接检眼镜检查疾病，是一种快速有效的方法 该方法显着减少了通过昂贵的费力筛选的需要 组织学方法。这些小鼠模型已显着增加 我们对色素性视网膜炎遗传性疾病的理解 人类的类别，并且可能在以下领域做出更重要的贡献： 即将到来的几年。 目前最广泛使用的突变被称为视网膜变性 (rd)、慢速视网膜变性 (rds)、浦肯野细胞变性 (pcd)、 和紧张（nr）。 我们将这些中的每一个都维持在几个遗传上 背景，包括三个独立发生的突变等位基因 PCD 轨迹。 我们已经开发或正在开发其中的大部分 菌株，并且是其中几种菌株的唯一持有者。 此外，我们 将为小鼠提供新的视网膜疾病，称为拥抱（拥抱）、白癜风 (vit) 和 wabbler lethal-2J (wl2J)；这些不仅影响视网膜 感光细胞，色素性视网膜炎类的标志 疾病，还会影响视网膜的其他组成部分，从而开放 加深我们对基因控制的理解的前景 视网膜色素上皮细胞和内核细胞的功能 神经节细胞层。 更多可用的突变体作为模型 先天性静止性夜盲症。 还有一些原因 色素沉着不足和轨迹发育异常 视神经中的神经节细胞轴突。 我们也准备好向其他调查人员提供建议，就像我们所做的那样 在这笔赠款的第一个资助周期中，关于突变体， 遗传背景、对照、年龄和小鼠数量可能有助于 解决他们的研究问题。 另一个服务功能是 关于突变体种群的繁殖和传播，包括 视网膜异常的转基因小鼠，是由其他人培育出来的 调查人员可能不希望独自承担扣留责任 并分发此类研究材料。