Extensions of MADM (Mosaic Analysis with Double Markers) in Mice
Figure 5
Cells with translocations and aneuploidy generated and labeled by MADM in vivo.
A) Schematic representation of cellular genotypes generated by interchromosomal recombination between non-homologous Chr. 6 and Chr. 10. In both chromosomes, the MADM cassettes are oriented in the telomere-to-centromere fashion. Each double-labeled cell contains the same reciprocal translocation, resulting in no net loss or gain of DNA. Single-labeled (green and red) cells exhibit abnormal copy numbers for parts of the chromosomes distal to the loxP sites: red cells are monosomic for the Chr. 6 portion and trisomic for the Chr. 10 portion; green cells have the reciprocal trisomy/monosomy. B) Representative confocal images of tissue sections obtained from R26GT/+;M10TG/+;HprtCre/Y mice. The sections were unstained or stained only with DAPI to label nuclei (blue, in the olfactory epithelium panel). The insets within the olfactory epithelium panel show examples of twin-spot labeling where red and green cells are located in close proximity. Due to the overall low frequency of labeling, each twin-spot labeling most likely originated from a single mitotic recombination event. Scale bars, panels: 100 µm, insets: 25 µm. C) Schematic representation of cellular genotypes generated by interchromosomal recombination between non-homologous Chr. 10 and Chr. 11. The MADM cassettes are oriented differently in the two chromosomes with respect to the corresponding centromeres. Each double-labeled cell contains the reciprocal translocation, resulting in one acentric and one dicentric chromosome. Single-labeled cells contain a dicentric or an acentric chromosome, and also exhibit abnormal copy numbers; the red cells are trisomic for Chr. 11 portion distal to loxP and monosomic for Chr. 10 portion proximal to loxP; the green cells are monosomic for Chr. 11 portion distal to loxP and trisomic for Chr. 10 portion proximal to loxP. D) Representative confocal images of unstained tissue sections obtained from M10TG/+;H11GT/+;HprtCre/Y mice. Scale bars, 100 µm.