Heterozygous Deletion of Mitotic Arrest–Deficient Protein 1 (MAD1) Increases the Incidence of Tumors in Mice
| Autor: | Akiko Miyazato, Kerstin Haller, Yan Li, Yoichi Iwanaga, Kuan-Teh Jeang, Jerrold M. Ward, Jean-Marie Peloponese, Ya-Hui Chi, Robert Benezra, Sergey Sheleg |
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| Přispěvatelé: | Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Claremont Graduate University [Claremont, CA ], Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Health |
| Rok vydání: | 2007 |
| Předmět: |
Male
Cancer Research Vincristine Mad1 Ratón Molecular Sequence Data Cell Cycle Proteins [SDV.CAN]Life Sciences [q-bio]/Cancer Haploidy Biology Genomic Instability Loss of heterozygosity Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Amino Acid Sequence Mitosis 030304 developmental biology Mice Knockout 0303 health sciences Nuclear Proteins Neoplasms Experimental Molecular biology 3. Good health Mice Inbred C57BL Disease Models Animal Oncology Mitotic spindle assembly checkpoint 030220 oncology & carcinogenesis Mad2 Proteins Knockout mouse Female Haploinsufficiency Gene Deletion medicine.drug |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2007, 67 (1), pp.160-166. ⟨10.1158/0008-5472.CAN-06-3326⟩ |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-06-3326 |
| Popis: | 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 Mad1+/− 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. [Cancer Res 2007;67(1):160–6] |
| Databáze: | OpenAIRE |
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