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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 ) [47, 125, 127]
H/H, H/− (*) Tumors in various tissues in ~50 % of 20 months-old mice NT p53+/− and p53−/− (); ApcMin/+ (colon ); Rb+/− (=); Pten+/− () [47, 125, 127]
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+/− (=) [44, 126]
Mad2 SAC +/− Lung tumors in 30 % of 18 months-old mice NT p53+/− () [45, 126]
overexp. Tumors in various tissues in 50 % of 12–20 months-old mice NT Eu-Myc (); KRASG12D () [30, 52]
Mad1; Mad2 SAC +/−; +/− NT NT p53+/− () [126]
BubR1 SAC +/− Not observed AOM-induced () ApcMin/+ (colon small intestine) [53, 57, 122]
H/H(*) Not observed DMBA-induced () p53−/− (incidence but shortened osteosarcoma latency and accelerated aging onset) [57, 134, 135]
overexp. Decreased DMBA-induced () KRASG12D () [50]
Bub3 SAC +/− Not observed DMBA-induced (=) p53+/− (=); Rb1+/− (=) [48, 49]
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 + (T-ALL) [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−/− (); Mad2+/− () [46, 59]
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−/− (); Atm−/− () [43, 125]
Pttg1 Securin, prevents chromatid separation −/− Testicular and splenic hypoplasia, thymic hyperplasia NT Rb+/− () [123, 136]
overexp. (transgenic mouse expressing human securin in pituitary cells) Hyperplasia and microadenomas NT Rb+/− (anterior lobe; intermediate lobe =) [137, 138]
  1. 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