Table 1.
Symbol | Name | Oncogenea | Key observations | Map |
---|---|---|---|---|
NCAT | N-terminal truncated ßcatenin |
Cre Off: Mars1 FAP Cre On: 1. ΔNßcat 2. ΔNßcat 3. ΔNßcat |
The positional recombination efficiency of Crainbow is biased 2.3-fold at position 1, 0.36-fold at position 2, and 0.32-fold at position 3. | Supplementary Fig. 4, Supplementary Data 1 |
MCAT | Multiple isoforms of ßcatenin |
Cre Off: Mars1 FAP Cre On: 1. ΔNßcat 2. Ccat/Lef1 3. ΔNßcatΔC |
Clone expansion occurs rapidly during perinatal development but is constrained by intestinal epithelial homeostasis in adult. | Supplementary Fig. 5, Supplementary Data 2 |
ROBO | RSPO3 Crainbow |
Cre Off: Mars1 FAP Cre On: 1. RSPO3 2. PTPRKe1:RSPO3e2–5 3. PTPRKe1–7:RSPO3e2–5 |
RSPO3 oncogenes expand the crypt microenvironment to induce crypt fission and promote rapid oncogenic clone spreading in the adult epithelium. | Supplementary Fig. 7, Supplementary Data 3 |
aDescription of oncogenes and Crainbow lines. (NCAT) ΔNßcat (aa. 80–781) is based upon the previously described N-terminal truncation mutant and escapes degradation to increase Wnt-signaling26. NCAT mice express ΔNßcat in positions 1–3 and are used to calculate positional bias in Crainbow transgenes. (MCAT) MCAT mice express three isoforms of ßcat that act as oncogene prototypes. ΔNßcat was directly compared with ßcat isoforms that possess an increased Wnt-signaling potential (Ccat/Lef1: aa.693-781/aa.57-398)33,34 or a decreased Wnt-signaling potential (ΔNßcatΔC, aa.80-693)33–35. MCAT mice are used to test the comparative ability of Crainbow modelling and measure oncogenic clone competition of three oncogenes. (ROBO) RSPO3 is expressed by the crypt microenvironment and controls stem cell homeostasis50. The recently described oncogenic fusions of PTPRKe1:RSPO3e2–5 and PTPRKe1–7:RSPO3e2–5 are known drivers of colorectal cancer16–18. ROBO mice are used to assess how oncogenic activation of microenvironmental cues could also be potent drivers of the rapid spread of premalignant clones in the adult intestinal epithelium. Oncogenes are pseudocolored to match the fluorescent protein barcode