Figure 3.

 Generation of Nf2 +/−;p53 +/− compound heterozygotes in cis and in trans. (A) Map of mouse chromosome 11, depicting the locations of the Nf2 and p53 loci, as well as the D11MIT20 SSLP marker used for allelotyping. (B) Scheme for the generation of Nf2 +/−;p53 +/− trans and cis mice. (C) Survival of mice carrying both Nf2 and p53 mutations either in cis on the same chromosome 11, or in trans, on opposite chromosomes 11, compared to the survival of either singly heterozygous parental strain. (D) Absence of both the Nf2 and p53 wild-type alleles in tumors from Nf2 +/−;p53 +/− cis mice. The same DNAs were digested with either StuI (for Nf2 LOH) or StuI plus EcoRI (for p53 LOH) restriction enzymes, and probed with a Nf2-specific probe (left) or a p53-specific probe [right; (pg) pseudogene]. Residual wild-type signals present in the tumor samples are likely the result of contaminating normal tissue. The intensities of residual wild-type p53 vs. wild-type Nf2 signals appear unequal here; however, most tumors exhibit equivalent levels of contaminating tissue. (E) Frequency of metastasis associated with Nf2-deficient or Nf2 plus p53-deficient osteosarcoma or fibrosarcoma.