International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 130 - THE GENERATION OF A TRANSGENIC MODEL FOR ZNF151 IN MOUSE

TL Harboe
Wilhelm Johannsen Centre for Functional Genome Research, Dept. of Medical Genetics, IMBG, The Panum Institute, University of Copenhagen

1) Tümer Z, 2) Jensen NA, 1) Tommerup N
1) Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Genetics, IMBG, The Panum Institute, University of Copenhagen (Denmark) 2) Experimental Molecular Genetics Laboratory, IMBG, The Panum Institute, University of Copenhagen (Denmark)

ZNF genes comprise one of the largest famillies of genes, several of which are associated with malignant disorder. ZNF151 and the murine homologue Zfp100, contain a POZ/BTB domain which obstruct the binding of nearby zinc finger domains to DNA.  ZNF151 was isolated and mapped to 1p36.1 – p36.2 by our group and has been shown to have a potent growth-reducing effect on HeLa cells. In a two-hybrid system ZNF151 interacts with MYC, disordered expression of which alters differentiation, cell-proliferation and -growth. Furthermore ZNF151 binds and transactivates adenovirus major late and cyclin D1 promotors. ZNF151 is therefore likely to be involved in important growth regulating pathways and is a candidate tumour-suppressor gene.To investigate the function of ZNF151 we are currently generating a mouse model, where Zfp100 is knocked out. Zfp100 was cloned and we have localised it to D4mit284. For this purpose we are creating a targeting vector, by which we will delete the largest part of the POZ/BTB domain, thereby destroying the binding site for MYC. As an additional study we are establishing siRNA-induced gene silencing in both human and mouse cell lines. siRNA studies seems to be a promising tool for reducing the expression of specific genes in mammalian cells. For this purpose we have identified siRNA targets for both genes, which will be cloned into pSUPER vectors, and then transfected into cell lines . The cell lines will later be examined for the expression of ZNF151/Zfp100, MYC and different MYC target genes such as TERT, CDK-4 and CDC25A.


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