Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice Journal Article
| Authors: | Iwanaga, Y.; Chi, Y. H.; Miyazato, A.; Sheleg, S.; Haller, K.; Peloponese, J. M. Jr; Li, Y.; Ward, J. M.; Benezra, R.; Jeang, K. T. |
| Article Title: | Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice |
| Abstract: | Mitotic arrest-deficient protein 1 (MAD1) is a component of the mitotic spindle assembly checkpoint. We have created a knockout mouse model to examine the physiologic consequence of reduced MAD1 function. Mad1+/- mice were successfully generated, but repeated paired mating of Mod1+/- with Mad1+/- mice failed to produce a single Mad1 animal, suggesting that the latter genotype is embryonic lethal. In aging studies conducted for > 18 months, Mad1+/- mice compared with control wild-type (wt) littermates showed a 2-fold higher incidence of constitutive tumors. Moreover, 42% of Mad1+/- (P < 0.03), but 0% of wt, mice developed neoplasia after treatment with vincristine, a microtubule depolymerization agent. Mad1+/- mouse embryonic fibroblasts (MEF) were found to be more prone than wt cells to become aneuploid; Mad1+/-, but not wt, MEFs produced fibrosarcomas when explanted into nude mice. Our results indicate an essential MAD1 function in mouse development and correlate Mad1 haploinsufficiency with increased constitutive tumors. ©2007 American Association for Cancer Research. |
| Keywords: | controlled study; gene deletion; nonhuman; cancer incidence; protein function; neoplasm; mouse; animals; cell cycle proteins; mice; mice, knockout; animal experiment; animal model; genotype; vincristine; mice, inbred c57bl; carcinogenesis; haplotype; nuclear proteins; amino acid sequence; molecular sequence data; fibrosarcoma; genomic instability; heterozygosity; neoplasms, experimental; fibroblast; mitosis spindle; aging; tumor growth; disease models, animal; aneuploidy; depolymerization; protein mad1; embryo mortality; haploidy |
| Journal Title: | Cancer Research |
| Volume: | 67 |
| Issue: | 1 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-01-01 |
| Start Page: | 160 |
| End Page: | 166 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-06-3326 |
| PUBMED: | 17210695 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 61" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus" |
