Abstract: The present invention relates to a novel class of gene trap vector (enhanced gene trap vectors, eGTV) for efficiently identifying silent or weakly expressed target genes in mammalian genomes, methods of their production and methods for identifying and mutating target genes by using the enhanced gene trap vectors. The gene trap vectors of the present invention can also be used for inducing the expression of silent genes and enhancing the expression of weakly expressed genes. The use of the enhanced gene trap vectors for creating transgenic organisms to identify gene function and to validate pharmaceutical compounds prior to clinical applications is a further aspect of the present invention.

Abstract: The present invention relates to a novel class of gene trap vector (enhanced gene trap vectors, eGTV) for efficiently identifying silent or weakly expressed target genes in mammalian genomes, methods of their production and methods for identifying and mutating target genes by using the enhanced gene trap vectors. The gene trap vectors of the present invention can also be used for inducing the expression of silent genes and enhancing the expression of weakly expressed genes. The use of the enhanced gene trap vectors for creating transgenic organisms to identify gene function and to validate pharmaceutical compounds prior to clinical applications is a further aspect of the present invention.

Abstract: The present invention relates to a non-human animal model, cell and tissue cultures derived therefrom, which do not produce or produce only suboptimal levels of one or more functional sestrins and in addition do not produce or do only produce suboptimal levels of latent transforming growth factor ? binding protein 4 (ltbp4). Furthermore, the present invention relates to a method for selecting agents for treating the pulmonary emphysema and/or the colorectal cancer exhibited by utilizing the animal model, cell or tissue culture of the invention. The animal model, cell or tissue culture is suitable for preclinical testing of efficacy, toxicity and bioavailability of potential agents.

Abstract: A transgenic mouse model for colorectal cancer, pulmonary emphysema or cardiomyopathy comprises a transgenic mouse that produces suboptimal levels of latent transforming growth factor ? binding protein 4 (LTBP-4). The transgenic mouse includes a mutation resulting in homozygous disruption of both endogenous alleles of a gene encoding LTBP-4, and develops colorectal cancer, pulmonary emphysema or cardiomyopathy.

Abstract: A new type of gene trap cassette, which can induce conditional mutations, relies on directional site-specific recombination systems, which can repair and re-induce gene trap mutations when activated in succession. After the gene trap cassettes are inserted into the genome of the target organism, mutations can be activated at a particular time and place in somatic cells. The gene trap cassettes also create multipurpose alleles amendable to a wide range of post-insertional modifications. Such gene trap cassettes can be used to mutationally inactivate all cellular genes temporally and/or spatially. Cells which contain the inventive gene trap cassette can be used for identification and/or isolation of genes and for the creation of transgenic organisms to study gene function at various developmental stages, including the adult, as well as for the creation of animal models of human disease useful for in vivo drug target validation.

Abstract: The present invention relates to plasmids or retroviral vectors comprising a human CD2 cell surface antigen fused in frame with a reporter gene and to methods of screening for a nucleic acid sequence encoding a protein comprising a signal sequence. In particular, methods are provided for screening for a nucleic acid sequence encoding a signal sequence protein that is regulated during a biological process.

Abstract: The present invention relates to an animal model and cells which do not produce functional latent transforming growth factor &bgr; binding protein 4 or which produce suboptimal levels of latent transforming growth factor &bgr; binding protein 4. Furthermore, the present invention relates to mehods and kits for diagnosing cancer, pulmonary emphysema or cardiomyopathy and analyzing whether cancer and/or pulmonary emphysema and/or cardiomyopathy are caused by a differential expression of LTBP-4 or by a defect in LTBP-4 gene. Moreover the present invention relates to selecting an agent for treating a sympton occurring in the animal model of the invention.

Abstract: The present invention relates to plasmids or retroviral vectors comprising a human CD2 cell surface antigen fused in frame with a reporter gene and to methods of screening for a nucleic acid sequence encoding a protein comprising a signal sequence. In particular, methods are provided for screening for a nucleic acid sequence encoding a signal sequence protein that is regulated during a biological process.

Abstract: The present invention relates to vectors for cancer therapy which as a result of genetic differences between normal and transformed cells selectively eliminate the latter. This is made possible by integrating a sequence-specific recombinase into a viral or non-viral expression vector whose expression is controlled by a transcription factor which has mutated in tumor cells and is therefore inactive, and also by a suicide gene which is flanked by at least one recombinase-specific target sequence. Through the transcription factor-mediated activation of the sequence-specific recombinase the vector is eliminated from untransformed cells together with the suicide gene. The vector is, however, not eliminated from tumor cells in which the transcription factor is inactive, and expresses the suicide gene. After contact with a corresponding prodrug these cells are selectively killed off.

Abstract: The invention under consideration concerns a gene-trapping construct containing a first reporter gene which after activation can activate a second reporter gene, and the use of this gene-trapping construct for identification and isolation of genes, especially genes transiently expressed. The invention under consideration furthermore concerns a cell, preferably a mammalian cell, containing the abovementioned gene-trapping construct. The invention under consideration in addition concerns the use of this mammalian cell for identification and/or isolation of genes, particularly transient genes. Furthermore the invention concerns a vector containing the abovementioned gene-trapping construct, as well as a kit for identification and/or isolation of genes, especially transient genes, that contains at least the abovementioned gene-trapping construct or the abovementioned vector.