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Donehower, Lawrence A.; Harvey, Michele; Vogel, Hannes; McArthur, Mark J.; Montgomery, Charles A.; Park, Sang H.; Thompson, Timothy; Ford, Richard J.; Bradley, Allan

Effects of genetic background on tumorigenesis in p53‐deficient mice

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  • Medientyp: E-Artikel
  • Titel: Effects of genetic background on tumorigenesis in p53‐deficient mice
  • Beteiligte: Donehower, Lawrence A.; Harvey, Michele; Vogel, Hannes; McArthur, Mark J.; Montgomery, Charles A.; Park, Sang H.; Thompson, Timothy; Ford, Richard J.; Bradley, Allan
  • Erschienen: Wiley, 1995
  • Erschienen in: Molecular Carcinogenesis
  • Sprache: Englisch
  • DOI: 10.1002/mc.2940140105
  • ISSN: 0899-1987; 1098-2744
  • Schlagwörter: Cancer Research ; Molecular Biology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Mice with disrupted germline <jats:italic>p53</jats:italic> alleles have been engineered by us and others and have been shown to have enhanced susceptibility to spontaneous tumors of various types. We monitored a large number of <jats:italic>p53</jats:italic>‐deficient mice(<jats:italic>p53</jats:italic>+/− and <jats:italic>p53</jats:italic>−/−) and their wild‐type littermates(<jats:italic>p53</jats:italic>+/+) of two different genetic backgrounds(129/5v and mixed C57BL/6 × 129/5v) up to 2 yr of age.<jats:italic>p53</jats:italic>+/− and <jats:italic>p53</jats:italic>−/− 129/Sv mice show accelerated tumorigenesis rates compared with their <jats:italic>p53</jats:italic>‐deficient counterparts of mixed C57BL/6 × 129/Sv genetic background. The tumor spectra of the two strains of mice are similar except that almost half of 129/Sv <jats:italic>p53</jats:italic>−/− males develop malignant teratomas, whereas these tumors are rarely observed in C57BL/6 × 129/Sv mice and never in 129/Sv p53+/− males. In the study reported here, we further characterized the lymphomas that arose in the p53‐nullizygous mice and found that over three‐quarters of the lymphomas were of thymic origin and contained primarily immature(CD4+/CD8+) T‐cells, whereas the remainder originated in the spleen and peripheral lymph nodes and were of B‐cell type. The high incidence of early‐onset lymphomas in the nullizygous mice makes these animals a good lymphoma model, whereas the heterozygous mice may be a useful model for Li‐Fraumeni syndrome, a human inherited cancer predisposition.© 1995 Wiley‐Liss, Inc</jats:p>