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- W1567231142 abstract "Establishing the functional significance of specific proteins has always been a major goal in pharmacology. The traditional approach of using inhibitors or antagonists has been helpful, but their limited availability and selectivity have hindered the overall utility of this approach. The advances in molecular biology have now provided new approaches capable of overcoming these problems. These advances have greatly simplified the manipulation of deoxyribonucleic acid (DNA) and enabled the generation of mice in which specific genes have been disrupted. Commonly termed “knockout mice,” these animals have been widely used. However, they do pose several problems. If the gene in question is crucial in development, the disruption may be lethal. Another more subtle problem has been the appearance of compensatory changes in other systems that can take over the role of the lost protein. Although these observations can be interesting, they make simple correlations between the absence of protein and behavior difficult. Finally, knockout mice are costly in terms of resources and time. The central nervous system (CNS) has proved amenable to antisense paradigms. Analgesic systems have been particularly sensitive owing to a number of factors such as their proximity to the ventricular system and the ability to discern, easily and functionally, modest changes in protein levels. The studies of these systems have identified a number of factors that may play a significant role in the overall success rate of antisense paradigms. Equally important is a method that has been developed for selectively assessing the functional activities of splice variants of a single gene. The selectivity of these approaches far exceeds that of traditional antagonists and can provide valuable insights into the functioning of the nervous system." @default.
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- W1567231142 date "2000-01-01" @default.
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- W1567231142 title "[4] Antisense mapping: Assessing functional significance of genes and splice variants" @default.
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- W1567231142 doi "https://doi.org/10.1016/s0076-6879(99)14094-1" @default.
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