Importantly, developed focal lesions along the femoral diaphysis compatible with periostal osteosarcoma, lesions observed in one mice as early as 3d of age. It is worth noting that in contrast with those previous observations, we did not detect any lesions compatible with spontaneous osteosarcomas in any of the Wwox KO mice analyzed macroscopically, histopathologically and radiographically. Furthermore, none of the long bones that were subjected to MicroCT analyses revealed any malignant lesions either. The reason for the discrepancies between studies remain to be determined. Very recently a spontaneous mutation in the Wwox gene was identified in rats that showed severe growth retardation, experienced epileptic seizures and died without reaching maturity. The mutation, named lde for lethal dwarfism with epilepsy, was identified as a 13-bp deletion in Exon 9 of the gene resulting in a frame shift mutation causing aberrant amino acid sequences at the C-terminal of the protein. Remarkably, lde/lde rats displayed phenotypic characteristics similar to mice including severe dwarfism and early lethality. The cause of dwarfism is not clear, however, lde/lde rats had slightly lower bone density and no osteosarcomas developed during their short life span. Interestingly, displayed significantly higher levels of BUN compared to normal rats consistent with the blood chemistry. In conclusion, we have generated a novel mouse model with a conditional allele at the Wwox locus. We demonstrated that homozygous Cre-recombinase mediated deletion of Wwox Exon 1 lead to complete ablation of Wwox expression. Loss of Wwox expression by this approach resulted in a phenotype similar to the previously reported generated by conventional techniques making this strain an important reagent for studying Wwox function in normal mouse physiology and tissue specific tumorigenesis. Considering that most of the studies have been conducted using tissue obtained from the primary tumor whereas EGFR monoclonal Grosvenorine antibodies have been used to treat the metastatic disease, it is Rostafuroxin possible that the lack of efficacy and/or the emergence of subsequent resistance may be due to genetic diversification of metastatic cells compared to their primary tumor counterparts or to dynamic variations in tumor genotype or phenotype that emerge during treatment.