Abstract: Embodiments of the present invention describe a novel and versatile inducible binary expression system (the ‘Q system’) and methods for controlling transgene expression in vitro and in vivo, for lineage tracing, for genetic mosaic analysis and for determining gene function.

Abstract: Recombination in mammalian somatic cell chromosomes is promoted and marked by a method called mosaic analysis with double marker (MADM). Mouse “knock-in” techniques are used to create pairs of chromosomes in which recombinase target sites are placed at homologous chromosomal locations. The knock-in constructs are engineered so that cellular markers, such as green or red fluorescent protein (GFP or RFP), are only expressed after recombinase-induced recombination. This system provides high-sensitivity detection of recombinase-induced mitotic recombination, even down to the single cell level. When this recombination is induced in a mouse heterozygous for a mutation in a gene distal to the “knock-in” locus on the same chromosome, it results in homozygosity of this mutation in the labeled cells. This allows the analysis in singly-labeled neurons of genes whose pleiotropic effects might otherwise result in early lethality.

Abstract: Reduced degeneration of an axon predetermined to be subject to degenerative neuropathy in a term patient is effected by contacting the axon in situ with an effective amount of a ubiquitin-proteasome system (UPS) inhibitor sufficient to reduce degeneration of the axon; and detecting a resultant reduction in the degeneration of the axon in situ.

Abstract: Reduced degeneration of an axon predetermined to be subject to degenerative neuropathy in a term patient is effected by contacting the axon in situ with an effective amount of a ubiquitin-proteasome system (UPS) inhibitor sufficient to reduce degeneration of the axon; and detecting a resultant reduction in the degeneration of the axon in situ.

Abstract: Reduced degeneration of an axon predetermined to be subject to degenerative neuropathy in a term patient is effected by contacting the axon in situ with an effective amount of a ubiquitin-proteasome system (UPS) inhibitor sufficient to reduce degeneration of the axon; and detecting a resultant reduction in the degeneration of the axon in situ.

Abstract: Recombination in mammalian somatic cell chromosomes is promoted and marked by a method called mosaic analysis with double marker (MADM). Mouse “knock-in” techniques are used to create pairs of chromosomes in which recombinase target sites are placed at homologous chromosomal locations. The knock-in constructs are engineered so that cellular markers, such as green or red fluorescent protein (GFP or RFP), are only expressed after recombinase-induced recombination. This system provides high-sensitivity detection of recombinase-induced mitotic recombination, even down to the single cell level. When this recombination is induced in a mouse heterozygous for a mutation in a gene distal to the “knock-in” locus on the same chromosome, it results in homozygosity of this mutation in the labeled cells. This allows the analysis in singly-labeled neurons of genes whose pleiotropic effects might otherwise result in early lethality.

Abstract: Reduced degeneration of an axon predetermined to be subject to degenerative neuropathy in a term patient is effected by contacting the axon in situ with an effective amount of a ubiquitin-proteasome system (UPS) inhibitor sufficient to reduce degeneration of the axon; and detecting a resultant reduction in the degeneration of the axon in situ.