Merck's Knockout Deal on Research Mice

For some scientists, a new bank may prove more popular than their local credit union. The Merck Genome Research Institute has unveiled a plan to give Lexicon Genetics Inc.--a biotech firm based in The Woodlands, Texas--$8 million to create 150 new strains of "knockout" mice, using a new technology the company has developed. The knockout mice, which will be made available to academic researchers at low cost, should help efforts to figure out what newly discovered genes do in the body.

Currently, it takes up to 10 months--and as much as $100,000--to develop a knockout mouse strain. As a result, only about 1000 knockouts now exist. Lexicon's solution is to create a bank of genetically altered mouse cells that can quickly be used to develop knockout strains. Company scientists first transfer a small bit of DNA into embryonic stem cells. This DNA will insert randomly into the DNA of the cells, disrupting any gene it happens to hit. The inserted DNA both knocks out the gene and, along with some adjacent mouse DNA, becomes a unique sequence tag marking that gene.

During the next 3 years, Lexicon will put high-throughput robots to work generating 500,000 mutant mouse embryonic stem-cell clones. Lexicon expects to have 50,000 clones in the freezer by the end of this year. Anyone with a new gene sequence could then pay to have Lexicon search through its computerized database of sequence tags--called OmniBank--to find any clones with an insert in that gene. Cells from those clones can then be thawed and used to create the appropriate knockout mouse strains, a procedure that should take just 4 to 6 months rather than the usual 6 to 10, says Arthur Sands, Lexicon's president. In addition, the Merck institute--a nonprofit foundation set up by the giant drug company--is pulling together a committee of six prominent biologists who will select 150 clones for development into mouse strains over the next few years.

Lexicon and Merck have promised to make these mice available to academic researchers at nominal cost, no strings attached. "Many labs have the expertise that would allow them to exploit knockout mice, but the main hurdle has been the cost," says endocrinologist Joseph Majzoub of Children's Hospital in Boston. "I think [the program] is an excellent idea."