Published online 26 September 2003 | Nature | doi:10.1038/news030922-16


First cloned rats born

Genetically identical rodents may help pinpoint gene function.

Two cloned rats were born from 130 implanted embryos.Two cloned rats were born from 130 implanted embryos.© Science

The humble lab rat has been cloned1. Ten-month-old rodent Ralph joins the growing list of celebrity doubles that includes Dolly the sheep and Cc the cat. It is hoped that cloned rats will help unravel genetics of human disease.

The technology will enable researchers to alter rat genes at will. "Our objective now is to use cloning to produce genetically modified rats," says Jean-Paul Renard from the French Institute for Agronomy Research, Jouy en Josas, France. The animals could model human disorders such as hypertension, diabetes and cancer.

"This will help to confirm the identity of genes involved in specific diseases," says developmental biologist John Mullins from Edinburgh University. Rats are also commonly used to study the brain and behaviour.

Rats have been difficult to copy. The standard method - where adult DNA is injected into an empty egg and then coaxed into life - doesn't work. Removed from an animal, rat eggs start multiplying before new DNA can be added. The unfertilised cells divide a few times, then die off.

Renard's team grew rat eggs in a culture dish with a drug that prevents cell division, then followed the normal procedure. They implanted 130 embryos into two surrogate mothers, yielding two healthy pups. Ralph, the first and the only named rat clone, is now father to a litter of healthy 2-month-old pups.

"It's a neat technological step," says cloning pioneer Ian Wilmut from the Roslin Institute, Edinburgh. The success rate, though low, is comparable to that in other species, such as sheep and horses. A third clone died shortly after birth. "Problems can crop up at any time," warns Wilmut, so animals must be monitored closely.

The research illustrates how methodological tweaks can influence cloning success between species. The new trick has worked in one rat strain, but many varieties are used in medical research. "We now need to show this is applicable to a wide variety of strains," says Mullins.

Rat race

Genetically modified rats can be produced by other methods, but their DNA is altered at random. Cloning gives added control - specific genes in the donor cell can be altered, added, or removed.

“Problems can crop up at any time.”

Ian Wilmut
Roslin Institute

"These are complementary techniques - both have their pros and cons," says Michael Gould from the University of Wisconsin-Madison who made the first GM rat. Genetically modified, cloned rats take longer to make and suffer more ill health, he points out.

Small rodents have been used in medical research for over a century. Mice gained popularity during the 1980s when researchers developed the ability to manipulate the mouse genome at will - resulting in some 5000 GM strains. Rat researchers may now play catch up. 

Roslin Institute

  • References

    1. Zhou, Q. et al. Generation of fertile cloned rats using controlled timing of oocyte activation. Sciencexpress, published online, doi:10.1126/science.1088313 (2003).