TRANSGENIC ANIMAL MODEL FOR SPLICEOSOME-MEDIATED RNA TRANS-SPLICING

摘要

The present invention relates to development of an animal model system for i n vivo testing of spliceosome-mediated RNA trans-splicing reactions. The prese nt invention provides transgenic animals, and methods for generating such animals, that have been genetically engineered to expresses a target precurs or messenger RNA molecule (target pre-mRNA) that serves as a substrate for a trans-splicing reaction. Specifically, the transgenic animals contain at lea st one transgene capable of expressing a target pre-mRNA molecule. The inventio n provides methods, based on utilization of the transgenic animals, for assessing the specificity and efficiency of a pre-trans-splicing molecule (PTM) designed to interact with a target pre-mRNA and mediate a trans-splici ng reaction resulting in the generation of a novel chimeric RNA molecule. The present invention further relates to the transgenic expression of PTM molecules in animals to determine gene function, i.e, functional genetics. T he present invention is based on the successful generation of a transgenic anim al expressing a target pre-mRNA and, moreover, the use of that animal to detect accurate in vivo trans-splicing reactions in the presence of a PTM.