Abstract: The present invention relates to homogenous fluorescence-based assays for measuring mitochondrial membrane potential in vertebrate cells. The assays use an inner filter such as Brilliant Black BN to quench non-specific fluorescence. The assays are particularly suited for ultra high-throughput screening for activators of mitochondrial uncoupling proteins, chemical uncouplers, compounds with mitochondrial toxicity, and compounds which stimulate mitochondrial biogenesis.

Abstract: Transgenic non-human mammals which express in their brains a nucleic acid construct comprising a DNA sequence encoding a human amyloid precursor protein FAD variant where at amino acid position 717 valine is substituted by isoleucine. These transgenic non-human mammals can be assays systems for determining compounds which are effective in modulating production of human amyloid precursor protein in brain and in isolated neuronal cells. Specifically exemplified are transgenic mice whose genome comprises a DNA sequence encoding a human amyloid precursor protein FAD variant where at amino acid position 717 valine is substituted by isoleucine operably linked to a Thy-1 promoter. The mice are shown to produce the APP-FAD variant in their brains by mRNA and protein assays.