Mouse library coming soon: Order any genetic mutant your study needs

Our knowledge of diseases come from rodents specially engineered to lack certain genes. And there's a huge global effort to achieve the ability to knock out every single mouse gene imaginable.

The largest international biological research initiative since the Human Genome Project is nearing completion…

Soon, every mouse gene will be disabled (or disable-able).
Scientists will engineer all sorts of mice missing all sorts of genes.
And we’ll be able to use those mutant mice to study the genetics of human diseases – and develop more drugs and test more therapies. Whoa.

Launched in 2006, the global effort’s goal is to disable each of the 20,000 or so genes in the mouse genome and make all the resulting stem cell lines available to the scientific community. Nature News reports.

"This resource will be of enormous benefit, not just to the mouse genetic community but to every scientist, every company looking at mammalian physiology, and of course everyone who wants to design better drugs and better healthcare," says Steve Brown, director of the Mammalian Genetics Unit at MRC Harwell. "It is one of the most significant biological resources in the past century of science, and I don't think I'm overstating the case here."

Researchers typically spend years engineering mice to lack specific genes – the ubiquitous ‘knockout mice’ – so they can model human diseases that involve those genes. This was slow, laborious, and fragmentary. And there wasn’t even an easy way to share the animals with other researchers afterwards.

So the International Knockout Mouse Consortium (IKMC) set out to create a library of mouse embryonic stem cell lines representing every possible gene knockout. After distribution to researchers, mutant mice can be generated from the cell lines and used for further study.

This is made possible by a new technology, published in Nature this week, pioneered by researchers at the Wellcome Trust Sanger Institute.

Using a high-throughput gene-targeting pipeline that allowed them to precisely engineer hundreds of genes every month, the team has inactivated more than 9,000 genes. They’re on track to knock out 7,500 more in the next few years.

Each knockout in their library contains an added ‘conditional’ allele (an allele is one form of a gene, a member of a pair). What it means is that, scientists can disrupt gene function in a living mouse at any body site and at any point in the animal's development by the timely addition of enzymes. That way, the effects of the missing gene won’t kill the mouse before its studied.

Other groups using ‘non-conditional’ techniques have inactivated thousands more genes. Regeneron Pharmaceuticals, for example, has specifically targeted around 3,500 genes.

Five years and over $100 million later, nearly 17,000 different genes have been knocked out. So there’s only around 3,000 more to go. (No problem.)

Already, mutant mice have been generated from almost 1,000 of the embryonic stem cell lines obtained, and the IKMC repositories in the US, Canada, and Europe receive hundreds of new orders every month.

The next challenge is to study the function of each missing gene. The National Institutes of Health last year committed $110 million over the next 5 years to characterize 2,500 of the IKMC's mutant mice through the International Mouse Phenotyping Consortium (IMPC).

And just so you know, knocking out genes in mice is easy… compared with figuring out what all those genes do.

Via Nature News.

Images: Library Mouse by lslc.specialservices, mouse on book by amanda's autopsies via Flickr

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