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A breakthrough in transgenic rats for biomedical research

The development of transgenic mice technology has greatly advanced over the years, and the use of transgenic mice in research has dramatically increased for the past two decades. The development of transgenic rats, on the other hand, has encountered many hurdles due to limited knowledge of rat reproductive physiology, and sensitivity and frailty of rats’ fertilized eggs under in vitro conditions. These limiting factors have constrained and delayed the development of predictable and reproducible production technology of transgenic rats, thus the application of transgenic rat models in research.

Recently, the scientists of the NARL’s National Laboratory Animal Center (NLAC) have employed a newly-developed transgenic rat technology to insert a specially-designed regulator gene construct that expresses ubiquitously. This is the world’s first technology platform that produces transgenic rats with a regulatory transgene, which is able to control the expression of red-green fluorescent protein gene (as a reporter gene) that also has been inserted into the transgenic rat. This regulatory transgene tus red-green fluorescent protein gene on or off, like a switch, thus affects red-green fluorescence intensity ratio. The scientists can then monitor the expression of particular genes by way of variations in the position and brightness of the red-green fluorescence in transgenic rats.

By using this newly-developed technology platform, a promising animal model with better simulation of different human ailments can be created and used in gene tracking to accurately assess disease onset and progression, and develop treatments and cures. And by monitoring real-time fluorescent color changes in transgenic rats, the scientists can use the method in drug discovery through the identification of novel drug targets, validation of those targets and screening for new therapeutic compounds. The method entailed will be accurate, rapid, non-invasive, and non-destructive (i.e. without sacrificing the animal). Moreover, given that rats are physiologically more similar to humans than are mice, transgenic rat models are superior to transgenic mouse models for use in pre-clinical animal experiments in the development of new drugs. Also their larger size makes rats more conducive to study human cardiovascular diseases, neurodegenerative diseases, metabolic diseases, reproductive disorders, memory and leaing behavior, diabetes, osteoporoses, etc.

The NARL-NLAC’s recent scientific breakthrough opens up novel possibilities to boost Taiwan’s biotechnology research and development, thereby the country’s competitiveness in biotechnology industry. In the future, the NARL-NLAC is to produce a large scale of transgenic rat lines that carry various disease genes tailored to meet the customer's requirements and expectations. These transgenic rat lines will be distributed by the NARL-NLAC’s Rodent Model Resource Center to the scientists at home and abroad to facilitate the development of new drugs and the translational medical research.