Table 1 Cancer phenotypes of CIN mouse models
From: Aneuploidy and chromosomal instability in cancer: a jackpot to chaos
Gene | Mitotic Function | Cancer phenotype of resulting mice | References | |||
|---|---|---|---|---|---|---|
Genotype | Spontaneous tumors | Chemically-induced tumors | Crossed with tumor-prone backgrounds | |||
Bub1 | SAC | +/− | Not observed | DMBA-induced ( | p53+/− and p53−/− (=); ApcMin/+ (colon | |
H/H, H/− (*) | Tumors in various tissues in ~50 % of 20 months-old mice | NT | p53+/− and p53−/− ( | |||
overexp. | Tumors in various tissues in 60-70 % of 12–16 months-old mice | NT | NT | [51] | ||
Mad1 | SAC | +/− | Lung tumors in 19 % of 18 months-old mice | Vinicristine-induced ( | p53+/− (=) | |
Mad2 | SAC | +/− | Lung tumors in 30 % of 18 months-old mice | NT | p53+/− ( | |
overexp. | Tumors in various tissues in 50 % of 12–20 months-old mice | NT | Eu-Myc ( | |||
Mad1; Mad2 | SAC | +/−; +/− | NT | NT | p53+/− ( | [126] |
BubR1 | SAC | +/− | Not observed | AOM-induced ( | ApcMin/+ (colon | |
H/H(*) | Not observed | DMBA-induced ( | p53−/− ( | |||
overexp. | Decreased | DMBA-induced ( | KRASG12D ( | [50] | ||
Bub3 | SAC | +/− | Not observed | DMBA-induced (=) | p53+/− (=); Rb1+/− (=) | |
Rae1 | SAC | +/− | Not observed | DMBA-induced (=) | NT | [48] |
Bub3; Rae1 | SAC | +/−; +/− | Not observed | DMBA-induced ( | NT | [48] |
Mps1 | SAC | DK/DK (**) | Not observed | NT | p53fl/+ Lck-Cre + ( | [128] |
DK/fl (**) | NT | NT | p53fl/fl Lck-Cre + (=) | [128] | ||
CENP-E | Chromosome congression, SAC | +/− | Lung and/or spleen tumors in 20 % of 19-21month mice but decreased incidence of liver tumors | DMBA-induced ( | p19/ARF−/− ( | |
Fzr1 (Cdh1) | APC/C cofactor | +/− | Mammary gland and other epithelial tumors in 25 % 20-30month mice | DMBA/TPA-induced skin carcinomas ( | NT | [42] |
Cdc20 | APC/C cofactor | +/AAA (***) | Hepatomas and lymphomas in 50 % of 24 month mice | NT | p53−/− ( | |
Pttg1 | Securin, prevents chromatid separation | −/− | Testicular and splenic hypoplasia, thymic hyperplasia | NT | Rb+/− ( | |
overexp. (transgenic mouse expressing human securin in pituitary cells) | Hyperplasia and microadenomas | NT | Rb+/− (anterior lobe | |||
)
)
); ApcMin/+ (colon
); Rb+/− (=); Pten+/− (
)
)
)
); KRASG12D (
)
)
)
small intestine
)
)
incidence but shortened osteosarcoma latency and accelerated aging onset)
)
)
)
T-ALL)
)
); Mad2+/− (
)
)
); Atm−/− (
)
)
; intermediate lobe =)- Lck-Cre: a Cre recombinase expressed under the control of the Lck (lymphocyte protein tyrosine kinase) promoter, promoting excision in a thymocyte-specific manner; (*) H: hypomorphic allele; (**) DK: kinetochore binding mutant; (***) AAA: Mad2 binding mutant; NT: not tested; (
) increased tumor formation; (
) decreased tumor formation; (=) no changes in tumor formation
) increased tumor formation; (
) decreased tumor formation; (=) no changes in tumor formation