Abstract: Described is the use of a non-human transgenic animal, preferably a mouse, characterized in that it contains a modified version of the gene encoding TIF-IA (a) as an animal model for a disease, (b) for analyzing the function of selected stem cells or (c) for ablating malignant cells or microglia cells. Furthermore, methods for screening a therapeutic compound are described which comprise administering a candidate compound to said non-human transgenic animal (or a cell line derived from said non-human transgenic animal) and monitoring a therapeutic effect of said compound.

Abstract: The present invention relates to an RNA polymerase I transcription factor TIF-IA and proteins related thereto, whose concentration and/or activity are correlated with the cell proliferation rate, and to DNA sequences encoding these proteins. The present invention also concerns ligands binding to an RNA polymerase I transcription factor TIF-IA and proteins related thereto, respectively, antagonists as well as antisense RNAs and/or ribozymes, directed against the TIF-IA expression. These compounds are of use for the prevention or treatment of diseases associated with an increased or reduced cell proliferation.

Abstract: Inactive transcription factor TIF-IA and uses thereof. Described are inactive forms of the human transcription initiation factor TIF-IA, preferably a mutant form of TIF-IA which lacks functionally important posttranslational modifications, e.g. phosphorylation, acetylation, glycosylation etc. Moreover, nucleic acid molecules encoding said TIF-IA are described as well as recombinant vectors containing said nucleic acid molecules, host cells and transgenic non-human animals. Various therapeutic uses are also described which are based on the finding that ribosomal transcription depends on a properly modified TIF-IA and that by blocking, e.g. the phosphorylation of TIF-IA, cell proliferation, e.g. proliferation of cancer cells can be reduced or inhibited.

Abstract: The present invention relates to an RNA polymerase I transcription factor TIF-IA and proteins related thereto, whose concentration and/or activity are correlated with the cell proliferation rate, and to DNA sequences encoding these proteins. The present invention also concerns ligands binding to an RNA polymerase I transcription factor TIF-IA and proteins related thereto, respectively, antagonists as well as antisense RNAs and/or ribozymes, directed against the TIF-IA expression. These compounds are of use for the prevention or treatment of diseases associated with an increased or reduced cell proliferation.

Abstract: The present invention relates to an expression vector having a foreign DNA. Said DNA at its 3′ end has a sequence which prevents the replication of the expression vector from occurring in the opposite direction to the transcription thereof. The invention also relates to a preparation containing such an expression vector and to the use of both in the permanent expression of foreign DNA in cells.