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FRIBIO-Biologi og biomedisin

Modeling human disease in mice;DNA repair and genomic (in)stability.

Tildelt: kr 3,4 mill.

Our research is currently focused on two classes of enzymes involved in repair, and possible regulation, of DNA and RNA species; flap endonuclease 1 (FEN1) and mammalian alkB homologs (ABHs). Genetic models are generated in order to elucidate the contribu tion of single gene deletions in genomic (in)stability, ageing and ageing related diseases such as cancer. We have recently succeeded in the construction of 6 new mouse models for these genes, providing an excellent opening phase of the projects. The init ial molecular characterization of two of these (ABH2 and ABH3) was recently published (Ringvoll et al., EMBO j., 2006, 25, 2189?2198). This application describes further work to characterize the possible role of ABH3 for RNA repair, and strategies to reve al the function of ABH1. Deletion of the ABH1 locus cause non-mendelian inheritance of disease (unpublished data). The design of genetic models for the exciting ABH8 gene is also described. The protein encoded by ABH8 contain domains for RNA binding, deme thylation and methylation. FEN1 mutated mice are being further studied to reveal the cause of high incidence of lymphomas. One of the additional motivating aspects of the making of genetic models is the network of nationally and internationally collabora tors enthusiastic on setting up collaborations. Central partners for the two projects discussed on the next pages are listed below, and future plans for the ABH (A) and, more briefly, the FEN1 (B) projects are described individually on the subsequent page s.

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FRIBIO-Biologi og biomedisin

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