MADM-GR mice are viable with no gross behavioral or observable abnormalities. Homozygous mice have low fertility, while heterozygous mice have no reported fertility defects. These mutants are designed for MADM (mosaic analysis with double markers), and must be crossed to mice harboring a reciprocal mutation at the same locus (see Stock No. 006067 or Stock No. 006080, MADM-RG (Dsred2/EGFP)). The resulting offspring have one copy of each reciprocal mutation on homologous chromosomes ("trans-heterozygous") and must next be bred to a Cre-expressing strain for fluorescent protein expression. Prior to Cre-recombination, double mutant mice do not have colored cells: the chimeric genes do not produce functional proteins because their coding sequences are interrupted by the beta-actin intron in different reading frames. After DNA replication (G2 phase) in double mutant mice, Cre-recombinase introduction that facilitates inter-chromosomal recombination aligns the respective N- and C-terminal coding sequences for each of the reporter genes on the same chromosome. The following chromatid segregation (X or Z) determines daughter cell phenotype (recombinant sister chromatids into the same daughter cell leads to double reporter expression [a G2-Z event], while independent segregation into separate daughter cells leads to expression of EGFP or Dsred2-MYC [a G2-X event]). If an additional targeted mutation of interest is introduced distal to the Gt(ROSA) locus, only homozygous cells will be singly labeled following G2 Cre-introduction. The homozygous mutant and wild type cells can then be distinguished by which single reporter they express. Reporter protein tissue specificity, expression levels, and frequency of recombination are thus determined by the promoter controlling Cre expression. Using this MADM system, a researcher can generate genetic mosaics in which an individual organism contains somatic cells of different genotypes. This allows the researcher to ascertain lineal relationships and pleiotropic gene function in multicellular organisms. These mice may also be useful in studies of cell differentiation and mitosis.

Mice harboring this MADM-GR mutation are also available on their original 129 genetic background (see Stock No. 006041). A control strain (Stock No. 006071, MADM-GG (EGFP/EGFP)) is also provided in which EGFP is in-frame on the same chromosome. Other important features of the MADM system are listed below. Cre-recombinase introduction in cell phase G0 or G1 results in double reporter expression. While EGFP expression can be visualized in vivo and in fixed samples, Dsred2-MYC can not. Anti-MYC immunofluorescence allows simultaneous visualization of both reporter genes. Single copy Dsred2-MYC is inadequate for live visualization.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.