Abstract: The present invention relates to a method of modifying a target sequence in the genome of a mammalian or avian oocyte by homologous recombination with a donor nucleic acid sequence, the method comprising the steps (a) introducing into the oocyte a zinc finger nuclease or a nucleic acid molecule encoding the zinc finger nuclease in expressible form, wherein the zinc finger nuclease specifically binds within the target sequence and introduces a double strand break within the target sequence; and (b) introducing a nucleic acid molecule into the oocyte, wherein the nucleic acid molecule comprises the donor nucleic acid sequence and regions homologous to the target sequence. The present invention further relates to a method of producing a non-human mammal or an avian carrying a modified target sequence in its genome.

Abstract: The present invention relates to a DNA molecule comprising: (a) a first DNA sequence comprising: (aa) a coding sequence giving rise upon transcription to a factor that contributes to the reprogramming of a somatic cell into an induced pluripotent stem (iPS) cell; (ab) a promoter mediating the transcription of said coding sequence; and (ac) two sequence motifs that mediate excision of (aa) and/or (ab) from the DNA molecule, wherein one sequence motif is positioned 5? and the other sequence motif is positioned 3? of the sequence to be excised; (b) a second DNA sequence comprising a sequence motif that mediates site-specific integration of (a) into another DNA molecule.

Abstract: The present invention relates to a fusion protein comprising a Caspase domain or a functionally active variant thereof and a ligand binding domain of a nuclear hormone receptor, a nucleic acid coding for the fusion protein, a vector or cell comprising the nucleic acid, a method of producing the fusion protein, a non-human transgenic animal containing the nucleic acid, the use of the fusion protein for ligand-mediated induction of apoptosis of a cell, or for studying the function of a cell, tissue and/or organ or the use of a transgenic organism for studying the function of a cell at various developmental stages or as a disease model, a method for inducing apoptosis of a cell expressing a fusion protein or for identifying a ligand, or a medicament comprising a fusion protein, the nucleic acid, the vector or the cell, particularly for the treatment of cancer or for or after transplantation, particularly as safety mechanism.

Abstract: The present invention relates to a combination of DNA segments comprising: (a) a first segment comprising in 5? to 3? or 3? to 5? order: (aa) a promoter; (ab) a first DNA sequence comprising: (i) a DNA sequence giving rise upon transcription to the sense strand of an shRNA molecule; (ii) a transcriptional stop element which is flanked by a first type of recombinase recognition sequences; and (iii) a DNA sequence giving rise upon transcription to the antisense strand of an shRNA molecule; (b) a second segment comprising in 5? to 3? or 3? to 5? order: (ba) a promoter; (bb) a second DNA sequence comprising: (i) a DNA sequence giving rise upon transcription to the sense strand of an shRNA molecule; (ii) a transcriptional stop element which is flanked by a second type of recombinase recognition sequences; and (iii) a DNA sequence giving rise upon transcription to the antisense strand of an shRNA molecule; wherein (i) said first type of recombinase recognition sequences are recognized and recombined by a recombinas

Abstract: The present invention relates to a method for identifying a compound capable of modulating an anxiety or depression disorder comprising the steps of: (a) contacting a composition comprising a B-Raf protein or a B-Raf gene in expressible form or a transcript thereof with a compound under conditions that allow for an interaction of the B-Raf protein or the B-Raf gene or a transcript thereof and the compound; and (b) measuring whether said interaction, if any, results in (i) a change of B-Raf kinase activity compared to B-Raf kinase activity in the absence of said compound; (ii) a modulation of the expression of the B-Raf gene compared to B-Raf gene expression in the absence of said compound; or (iii) the formation of a complex between the compound and the B-Raf protein, wherein such a change in activity, modulation of expression or the formation of a complex is indicative of the compound being a modulator of an anxiety or depression disorder.

Abstract: The present invention relates to a process that enables constitutive and inducible gene knock down in living organisms using a short hairpin RNA expression vector integrated into the genome of the organism.

Abstract: An improved and reproducible method for the generation of ES mice from inbred ES cells, without the need to generate a chimeric mouse intermediate is provided. The inbred ES cells may be recombinant or genetically modified, resulting in ES mice that are transgenic. The method may also be used for the fast production of ES mice strains homozygous for a defined genetic alteration.