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Patients with dominantly inherited Li-Fraumeni syndrome have a loss-of-function mutation in TP53 and develop diverse mesenchymal and epithelial neoplasms at multiple sites. Trp53  +/- female mice with the BALB/c background provide unique characteristics for the study of breast cancer in Li-Fraumeni syndrome; however, we previously found that female C3H- Trp53 +/   - mice did not spontaneously develop mammary tumors. Therefore, we obtained F1 and N2-N4 female mice by backcrossing the BALB/c strain and examined the incidence of mammary and other tumors in lifetime studies. Malignant lymphomas, osteosarcomas, and uterine adenocarcinomas spontaneously developed in approximately 20% or more of Trp53 +/   - mice with the C3H background. In contrast, the incidence of uterine adenocarcinomas showed a tendency to decrease, while that of mammary adenocarcinomas gradually increased in mice with the BALB/c strain backcross. Wild-type BALB/c female mice are predisposed to a wide spectrum of neoplasms, including mammary tumors, partly due to genetic factors, whereas uterine tumors are uncommon not only in BALB/c mice but also C3H mice. Thus, genetic factors appear to contribute to a strain-specific predisposition to malignant neoplasms in Trp53 +/-  mice, and further studies are needed to clarify the detailed mechanisms.

journal of toxicologic pathology

Increased susceptibility to mammary carcinogenesis and an opposite trend in endometrium in &lt;i&gt;Trp53&lt;/i&gt; heterozygous knockout female mice by backcrossing the BALB/c strain onto the background C3H strain