The present invention provides methods of using non-invasive imaging technologies to monitor the effects of potential therapeutic compounds on gene expression in non-human living animals. This invention also provides methods to analyze perturbation in biochemical pathways and physiological functions associated with disease (e.g. a cancer, cardiovascular disease, degenerative nervous system disease, osteoporosis, disease related to body weight regulation, toxicity, and any other disease condition related to abnormal gene expression) using the non-invasive imaging technologies to monitor alterations in gene expression in non-human living animals.

Use of non-invasive imaging technologies to monitor in vivo gene-expression

Methods of imaging distribution of myeloperoxidase activity in a subject are disclosed. These methods include the use of bioluminescent substrates, including luminol and wavelength-shifted analogues of luminol. Bioluminescent myeloperoxidase substrates that emit light at longer wavelengths compared to luminol are shown to be useful for imaging myeloperoxidase activity in vivo. The disclosed methods can be used for imaging sites of inflammation and other pathological conditions associated with abnormal levels of MPO activity in vivo. Methods of synthesis of luminol analogues are also disclosed.

Bioluminescence imaging of myeloperoxidase activity in vivo, methods, compositions and apparatuses therefor

Disclosed herein are methods of identifying inhibitors of gene silencing or re-silencing, which can include repressing expression of a selectable marker gene in mammalian cells, treating the cells with at least one test compound, growing the cells under selective conditions, and quantifying the relative number of cells that live, wherein a change in the relative number of cells as compared to cells that were not treated with the test compound, identifies the compound as an inhibitor of gene silencing or re-silencing. Also disclosed herein are transgenic mice and isolated cell lines that are useful in the disclosed methods and kits for use in performing the disclosed methods.

Methods of identifying inhibitors of gene silencing in mammalian cells

The technologies described herein are based on the discovery that expression of a toxin gene under control of an eosinophil-specific promoter can cause the ablation of eosinophils in a transgenic animal. Accordingly, the nucleic acid constructs featured in the invention are used to generate eosinophil-deficient transgenic animals that are useful for the study of pathologies and treatments relating to tissues and organ systems that typically contain eosinophils.

Eosinophil-deficient transgenic animals

The present invention provides methods and compositions for the effective treatment of gastro-intestinal dysfunction, including chronic and acute inflammatory bowel diseases and the symptoms thereof, through the modulation of eosinophil peroxidase activity. The methods and compositions disclosed include those that modulate eosinophil peroxidase activity by depleting substrate, antagonizing enzyme activity, or attenuating enzyme expression so as to effect treatment of disease conditions or symptoms. Also provided are methods for the identification of additional therapeutically effective compounds for the treatment of gastro-intestinal dysfunction through the modulation of eosinophil peroxidase activity.

Methods and compositions for treating eosinophil mediated gastro-intestinal dysfunction or disease

The present invention relates to novel transcription control elements derived from a mouse eosinophil peroxidase gene. The novel transcription control elements described in the disclosure may comprise isolated polynucleotides, expression cassettes, vectors, recombinant cells, and transgenic animals.

Transgenic mice comprising transcription control elements associated with mouse eosinophil peroxidase expression

The present invention relates to novel transcription control elements derived from a mouse eosinophil peroxidase gene. Such transcription control elements may comprise isolated polynucleotides, expression cassettes, vectors, recombinant cells, and transgenic animals, as described herein.

Isolation and identification of transcription control elements associated with mouse eosinophil peroxidase expression

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Transgenic mice comprising transcription control elements associated with mouse eosinophil peroxidase expression

Isolation and identification of transcription control elements associated with mouse eosinophil peroxidase expression