Figure 1: A five-month-old semi-cloned mouse.
last updated April 2013
An easier way to genetically modify mice
Haploid embryonic stem cells help create gene-targeted knockout mice with less fuss and greater reliability
© 2012 Jinsong Li, Chinese Academy of Sciences
The standard way of creating genetically engineered mice leaves much to be desired. First, biologists insert embryonic stem (ES) cells into early embryos. Then, they interbreed the resulting ‘chimeric’ mice to yield the occasional pup derived entirely from the introduced genetic lineage. But this process is “tedious and very inefficient,” says Jinsong Li, a stem cell researcher at the Chinese Academy of Sciences (CAS). So, Li set out to devise a simpler approach.
A team led by Li and Guoliang Xu, also at CAS, started by plucking out haploid ES cells from cloned embryos that were generated by inserting sperm heads into eggs with the nuclei removed. These stem cells contained just one set of chromosomes and retained chemical modifications characteristic of the paternal line, which meant they could be used in place of sperm to fertilize other eggs. In this way, the researchers obtained ‘semi-cloned’ mice (Fig. 1) and bred their offspring, half of which were derived entirely from the stem cell lineage1.
For mouse genetics, this approach is “fast and reliable,” notes Li. But the strategy could have broad utility in other species. “For many important large animals, such as monkeys, conventional ES cells have been established but they fail to support the production of chimeras,” he says.