U.S.-Argentina Cooperative Research: Conditional Gene Targeting of Brain Dopamine Receptors

9901278低这个美洲计划奖将资助一个为期三年的合作研究项目之间的马尔科姆低博士，Vollum研究所，俄勒冈州健康科学大学，波特兰，俄勒冈州，和博士马塞洛鲁宾斯坦，布宜诺斯艾利斯大学，阿根廷。 他们计划利用一种新技术，在成年小鼠的选择性大脑基质中产生多巴胺受体亚型的条件性敲除。 哺乳动物大脑中这些突变的目的是提供生理过程的实验控制。 在胚胎干细胞中通过同源重组产生无效等位基因是确定体内基因生理功能的有力技术。 然而，这种方法的缺点包括单个基因的多种功能的丧失和通过特定神经元中其他基因过程的表达变化的发育补偿。在这个项目中，研究人员将开发一种新技术来克服这些限制。 如果在多巴胺能系统中获得成功，同样的实验策略将普遍适用于大脑中表达的许多基因的功能分析。这两位研究人员是所采用技术的专家，因此这项工作将产生重要的新突变方法，小鼠品系和对多巴胺受体功能的见解。 这项研究的更广泛的影响包括，除了开发在中枢神经系统基因中产生局部条件突变的新方法外，还包括理解局部脑区中五种不同多巴胺受体亚型的功能意义 *

9901278LowThis Americas Program award will fund a three year cooperative research project between Dr. Malcolm Low, Vollum Institute, Oregon Health Sciences University, Portland, Oregon, and Dr. Marcello Rubinstein, Universidad de Buenos Aires, Argentina. They plan to utilize a new technology that will produce a conditional knockout of dopamine receptor subtypes in selective brain substrates of the adult mouse. The objective of these mutations in mammalian brain is to provide the experimental control of physiological processes. The generation of null alleles by homologous recombination in embryonic stem cells is a powerful technique to determine the physiological function of genes in vivo. However, drawbacks of this approach include the loss of multiple functions of a single gene and developmental compensation by changes in the expression of other genes processes in specific neurons. In this project the investigators will develop a new technology to overcome these limitations. If successful in the dopaminergic system, the same experimental strategy would be generally applicable to the functional analysis of many genes expressed in the brain.The two investigators are experts in the techniques to be employed, therefore significant new mutational approaches, mouse strains and insights into dopamine receptor function will result from this work. The broader impact of this research includes, besides the development of new methods to produce localized, conditional mutations in central nervous systems genes, the understanding the functional significance of the five different dopamine receptor subtypes in localized brain regions ***