International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 57 - AN OVERVIEW OF THE CELLTECH ENU MUTAGENESIS PROGRAM

Mark Appleby
Celltech R&D Inc.

1) Brunkow M, 1) Staehling Hampton K, 1) Charmley P, 1) Ramsdell F, 1) Bouck J, 1) Tang P, 1) McEuen M, 1) Paeper B, 1) Britschgi T, 1) Bennington A, 1) Proll S, 1) Bobick S, 1) Tittel P, 1) Wasnick M, 1) Snell A, 1) Palmberg G, 2) Carlson G, 1) Schatzman R
1) Celltech R&D Inc, 2) McLaughlin Research Institute

The Celltech ENU Mutagenesis program is focused primarily on identifying novel, clinically relevant targets in the areas of inflammation, autoimmunity and lymphocyte biology.  We have implemented a number of in vitro and in vivo screens designed to identify mutations specifically affecting the function of the immune system, including  activation of T- and B-cells, T-dependent and T-independent inflammatory responses, and mouse models of colitis and graft versus host disease.  Screening exclusively for recessive phenotypes, we have identified nearly 100 phenodeviants which have entered into the mapping process.  We have developed an integrated laboratory / informatic pipeline which enables rapid identification of a candidate interval and the genes contained within, as well as efficient tracking of gene testing results, capturing both exon sequencing and gene expression data.  Our development and utilization of informatics tools has proven critical in the effective management of the program.We maintain an ongoing process of developing new screens as well as continuously evaluating the ‘usefulness’ of current screens with respect to clinical relevance, heritability and ‘mappability’. The identification of missense mutations in known immunologically important genes can lead to a more detailed understanding of the function of specific domains and may even point toward an involvement in pathways not previously observed in conventional gene knock-out models.  We will present examples of these concepts using the mutants cloned in the program.


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