New technique creates targeted knockout rats

Scientists have created genetically modified rats with permanent heritable gene mutations, paving the way for the development of novel genetically modified animal models of human disease.

The researchers used zinc finger nuclease (ZFN) technology from US biotech outfit, Sigma-Aldrich Corporation, to knock out an inserted reporter gene and two native rat genes without causing measurable effects on other genes. These mutations were then shown to be permanent and heritable.

"Until now, rat geneticists lacked a viable technique for 'knocking out,' or mutating, specific genes to understand their function," said Howard Jacob, Director of the Human and Molecular Genetics Center at the Medical College of Wisconsin.

Rats are physiologically more similar to humans than are mice for many traits and are ideal subjects for modelling human diseases. Generating rats with knockout mutations has been a major challenge, but the new technique will increase the rat's usefulness in research pertaining to physiology, endocrinology, neurology, metabolism, parasitology, growth and development and cancer.

ZFNs are engineered proteins that induce double strand breaks at specific sites in an organism's DNA. Such double-strand breaks stimulate the cell's natural DNA-repair pathways and can result in site-specific changes in the DNA sequence. Previously, ZFNs were used to knock out specific genes in fruit flies, worms, cultured human cells and zebrafish embryos and are now in human clinical trials for the treatment of HIV/AIDS. This is the first example of successful gene editing in mammalian embryos using this technology.

The paper was published today in the journal Science.