Whole-body optical imaging of gene expression and uses thereof

A method to evaluate a candidate protocol or drug for treating a disease or disorder, which method comprises:

• a) administering said protocol or drug to a non-human mammalian subject which expresses a fluorophore under the direction of a promoter of a gene associated with said disease or disorder, and determining the expression of said gene via observing the presence, absence or intensity of the fluorescence generated by said fluorophore at various locations in said mammalian subject by whole-body external fluorescent optical imaging;
• b) determining the expression of said gene, via observing the presence, absence or intensity of the fluorescence generated by said fluorophore at various locations in said mammalian subject by whole-body external fluorescent optical imaging, in a control non-human mammalian subject which expresses said fluorophore under the direction of said promoter of said gene;
• and
• c) comparing the expression of said promoter determined in steps a) and b), wherein the expression determined in step a) is different from that in step b) identifies said protocol or drug as effective in treating the disease or disorder.

A method to screen for a modulator of the expression of a gene in a multi-cellular organism, which method comprises:

• a) administering a test substance to a non-human multi-cellular organism which expresses a fluorophore under the direction of a promoter of a gene, and determining the expression of said promoter via observing the presence, absence or intensity of the fluorescence generated by said fluorophore at various locations in said multi-cellular organism by whole-body external fluorescent optical imaging;
• b) determining the expression of said promoter, via observing the presence, absence or intensity of the fluorescence generated by said fluorophore at various locations by whole-body external fluorescent optical imaging, in a control multi-cellular organism which expresses said fluorophore under the direction of said promoter of said gene;
• and
• c) comparing the expression of said promoter determined in steps a) and b), wherein the expression determined in step a) is different from that in step b) when said test substance modulates said gene expression.

A method to screen for a multi-cellular organism that expresses a gene at an altered level, which method comprises:

• a) administering a mutation-inducing agent or treatment to a non-human multi-cellular organism which expresses a fluorophore under the direction of a promoter of a gene, and determining the expression of said promoter via observing the presence, absence or intensity of the fluorescence generated by said fluorophore at various locations in said multi-cellular organism by whole-body external fluorescent optical imaging;
• b) determining the expression of said promoter, via observing the presence, absence or intensity of the fluorescence generated by said fluorophore at various locations by whole-body external fluorescent optical imaging, in an untreated control multi-cellular organism which expresses said fluorophore under the direction of said promoter of said gene;
• and
• c) comparing the expression of said promoter determined in steps a) and b), wherein the expression determined in step a) is different from that in step b) when said multi-cellular organism expresses said gene at said altered level.