Pied piper in lab

Scientists devise genetically tweaked rats to study cancer

By Ishita Das
Published: Wednesday 15 September 2010

RATS and mice can mimic human diseases and hence are important laboratory models to understand causes of ailments as well as the efficacy of drugs. For some unknown reason rats are better candidates to understand certain diseases than mice. For example, explained Aron Geurts, physiology professor at Medical College of Wisconsin, USA, rats are better laboratory models for hypertension and kidney; mice do not develop these diseases. But mice have an advantage over rats: they are more amenable to genetic manipulation.

Since the 1980s scientists have been using this advantage to develop knockout mouse in which specific genes are knocked out so that their role can be studied by observing any differences from normal behaviour or condition. The technique involves growing embryonic stem cells in a dish, manipulating their genes and then implanting in a female to grow them into embryos. Developing knockout rats, however, gave researchers a hard time because their genetically manipulated embryonic stem cells did not grow into embryos well. Only in 2007 did the concerted effort of laboratories from USA and UK give rise to the technique to get around the problem. Using the technique, Qi- Long Ying, now at University of South California, USA, recently made the first knockout rat by striking off a widely studied tumour suppressor gene, p53. His research was published online in Nature on August 11.

The mouse knocked out for p53 gene has existed for decades. Do we still need a rat model? The p53 gene is significantly involved in causing breast cancer, said Michael Gould, professor of oncology in University of Wisconsin School of Medicine and Public Health, USA. Most mouse models do not simulate hormone dependent breast cancers, while rat models do, Gould said, calling knockout rats the Holy Grail of rat genomics. There is another advantage to it. “We can choose which model best represents the physiological or disease trait we are studying,” said Geurts.

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