Prof Karen Steel, Kings College London/Wellcome Trust Sanger Institute
Kat - Researchers at the Wellcome Trust Sanger Institute have published the first batch of results from an ambitious project aiming to systematically knock out, or delete, every single gene in mice, one at a time. Not only have the results provided a whole bunch of scientific surprises, but the scientists are creating an incredibly valuable resource for biomedical researchers around the world. Here’s Professor Karen Steel, lead researcher for the project, to explain more.
Karen - The Sanger Institute several years ago, set up a project called ‘The Mouse Genetics Project’ and the aim of this was to develop a large panel of new mouse mutants, each of them with a single gene targeted or mutated. Then with these mutants, we put them through a screening process to pick out a wide variety of different signs of different diseases, and also, variations in phenotype, normal aspect of the function of the mouse.
Kat - What sort of diseases were you looking at?
Karen - The whole range, ranging from hearing and deafness which is my personal interest, to metabolism, to vision defects, to general developmental defects that could affect the development and morphology of any part of the body, and fertility and viability, so a very wide range of things.
Kat - What did you find when you looked at all these mice doing all these things?
Karen - Well, we’ve just published the first analysis of the first 250 mouse lines that we’ve generated. One of the things that we found from that was that some of those genes were known, well known, and other genes were completely unknown and nothing had been published about them previously. What we found was that we were just as likely to find some phenotypes and aspect of the function of the mouse in these new genes, these novel genes that hadn’t been described properly before other than their sequence compared to the well-known genes.
So, what that tells us is there’s a lot of genes out there in the genome that nobody is paying attention to or studying. Really, they are likely to be a very rich resource for finding associations between genes and between function and particularly, between genes and diseases.
Kat - So, we need to look outside the usual suspects and start looking at all these other genes as well.
Karen - Absolutely, yes. Of course, some of the genes that we studied were ordinary and there have been papers published about them. But by doing systematic screen, putting every mouse line through the same battery of tests, we found new aspects of their phenotype that hadn’t been published before, that haven’t been found before. So, it gives them that fuller picture of what is likely to be going wrong as a result of a mutation in specific single genes.
Kat - So, you've looked at 250 different mouse mutations so far. How many more have you got to go and how long is that going to take?
Karen - Well, there are 20,000 genes approximately in the mouse genome.
Kat - A long time!
Karen - So, it’s going to take a while. At the Sanger Institute, we’ve generated over 900 mouse lines so far, so we’re getting along quite well. It’s still a long way to go before we get all of the genes. As we generate those mouse mutants, and breed enough mice to put through the screening, then the data from those new lines are going onto the website.
One of the really key aspects of this resource is that it’s a public resource. So, anybody can go and look on the website find all of the data about the phenotypes, the characteristics of these different mouse mutants. Scientists and clinicians can also get access to the mouse models themselves so that they can get that mouse into their own laboratory and do their own specialised tests because they're the experts in their own disease areas. And so, they're likely to be able to do a much more detailed analysis than we can do as part of a screen.
Kat - That was Professor Karen Steel - now at King’s College London but previously at the Wellcome Trust Sanger Institute where this research was done.