Knockout Mouse Project Approaches Midpoint

An international consortium of researchers has established a novel and efficient system for selective “knockout” of genes in mouse embryonic stem cells that is expected to become the foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.

Investigators at the Wellcome Trust Sanger Institute (Hinxton, United Kingdom) reported in the June 16, 2011, issue of the journal Nature that they had used computational allele design, 96-well modular vector construction, and high-efficiency gene-targeting strategies to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N mouse embryonic stem cells. In other words, they already have succeeded in knocking out almost 40% of the genes in the mouse genome.

Detailed information regarding vectors for these genes is being made available to the mouse research community through the consortium's web portal online (please see Related Links below).

Gene targeting is a directed approach that uses homologous recombination to mutate an endogenous gene. Specifically, this method can be used to delete a gene, remove exons, and introduce point mutations either permanently or in a conditional fashion. Gene targeting requires the creation of a specific vector for each gene of interest but can be used for any gene, regardless of transcriptional activity or gene size.

“We are producing mutations in embryonic stem cells with greater efficiency and speed than we predicted and at well above the historical average,” said senior author Dr. Allan Bradley, director emeritus of the Wellcome Trust Sanger Institute. “We have taken careful steps to ensure we deliver quality resources of maximum utility that will stand the test of time. Indeed, we expect our systems will be increasingly adopted by researchers using human and other cells to seek advances in the understanding of disease.”

Related Links:
Wellcome Trust Sanger Institute
Knockout Mouse Consortium