A Mouse for All Reasons

  title={A Mouse for All Reasons},
  author={Francis S. Collins and Janet Rossant and Wolfgang Wurst},
Three major mouse knockout programs are underway worldwide, working together to mutate all protein-encoding genes in the mouse using a combination of gene trapping and gene targeting in mouse embryonic stem (ES) cells. Although the current emphasis is on production of this valuable resource, there are significant efforts to facilitate program coordination, to enhance the availability of this resource, and to plan for future efforts in mouse genetics research. 

Paper Mentions

A New Partner for the International Knockout Mouse Consortium
A recent Commentary in Cell outlined the plans of three major programs in the US, Canada, and Europe to mutate all protein-encoding genes in the mouse using a combination of gene targeting and gene trapping in mouse embryonic stem (ES) cells. Expand
Bi-allelic gene targeting in mouse embryonic stem cells.
Inducible homozygous cells described here provide a precisely controlled experimental system to study gene function in a model cell and present a method for conditional ablation of genes in ES cells using vectors and targeted clones from the EUCOMM and KOMP conditional resources. Expand
Trends in large-scale mouse mutagenesis: from genetics to functional genomics
  • Y. Gondo
  • Biology, Medicine
  • Nature Reviews Genetics
  • 2008
The origins and rationale of large-scale mouse mutagenesis programmes are traced to develop a fundamental research infrastructure for mammalian functional genomics and to produce human disease models. Expand
Dual RMCE for efficient re-engineering of mouse mutant alleles
dRMCE is a scalable, flexible tool to introduce tags, reporters and mutant coding regions into an endogenous locus of interest in an easy and highly efficient manner. Expand
A conditional knockout resource for the genome-wide study of mouse gene function
High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome. Expand
The mammalian gene function resource: the international knockout mouse consortium
The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research. Expand
Identifying essential genes in mouse development via an ENU-based forward genetic approach.
An efficient and non-biased, N-ethyl-N-nitrosourea (ENU)-based forward genetic approach in mouse provides a unique tool for the identification of genes essential for development and adult physiology via ENU-based mutagenesis, which has become a powerful tool in deciphering gene functions. Expand
A review of current large‐scale mouse knockout efforts
The knockout mouse project (KOMP) and the international gene trap consortium (IGTC) were initiated to create convenient resources for scientific research worldwide and knock out all the mouse genes. Expand
Towards better mouse models: enhanced genotypes, systemic phenotyping and envirotype modelling
The mouse is the leading mammalian model organism for basic genetic research and for studying human diseases. Coordinated international projects are currently in progress to generate a comprehensiveExpand
Mouse mutants and phenotypes: accessing information for the study of mammalian gene function.
Methods to quickly obtain information on what mutant ES cells and mice are available are described, including recombinase driver lines for the generation of conditional mutants, to access genetic and phenotypic data that identify mouse models for specific human diseases. Expand


The Knockout Mouse Project
It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. Expand
The European dimension for the mouse genome mutagenesis program
The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish andExpand
A public gene trap resource for mouse functional genomics
It is concluded that gene trapping is an effective strategy to mutate a substantial fraction of the genes in mice that compares favorably with gene-targeting approaches. Expand
Genomewide production of multipurpose alleles for the functional analysis of the mouse genome.
This work has used these directional recombination vectors to assemble the largest library of ES cell lines with conditional mutations in single genes yet assembled, presently totaling 1,000 unique genes. Expand
A reliable lacZ expression reporter cassette for multipurpose, knockout‐first alleles
This work reports success with a “knockout‐first” strategy that ablates gene function by insertion of RNA processing signals without deletion of any of the target gene. Expand
High-throughput engineering of the mouse genome coupled with high-resolution expression analysis
The development of a high-throughput and largely automated process that uses targeting vectors based on bacterial artificial chromosomes (BACs) that permits genetic alteration with nucleotide precision, is not limited by the size of desired deletions, does not depend on isogenicity or on positive–negative selection, and can precisely replace the gene of interest with a reporter that allows for high-resolution localization of target-gene expression. Expand
Recombineering: a powerful new tool for mouse functional genomics
Recombineering facilitates many kinds of genomic experiment that have otherwise been difficult to carry out, and should enhance functional genomic studies by providing better mouse models and a more refined genetic analysis of the mouse genome. Expand
Gene targeting using a promoterless gene trap vector ("targeted trapping") is an efficient method to mutate a large fraction of genes.
It is reported that homologous recombination using a promoterless gene trap vector ("targeting trapping") yields targeting frequencies averaging above 50%, a significant increase compared with current approaches. Expand
A new logic for DNA engineering using recombination in Escherichia coli
A straightforward way to engineer DNA in E. coli using homologous recombination is described. The homologous recombination reaction uses RecE and RecT and is transferable between E. coli strains.Expand
As part of the course at York each person is given the task of creating a character to present to the rest of the group. About ten weeks are allowed for its growth but hardly any of the preparationExpand