Mouse Models of the Neu Ligand Interaction with its Receptor in Mammary GlandTumorigenesis and Development

摘要

To test if Neu differentiation factor (NDF), an activator of the c-neu gene, isproliferative or differentiative in the mammary gland, we have generated a transgenic mouse line overexpressing NDF in the mammary epithelium. These mice develop mammary adenocarcinomas in a stochastic fashion, develop Harderian gland hyperplasia and have subtle developmental abnormalities of the mammary gland. Together, these data point to a proliferative effect of NDF in the mammary gland and possibly an inhibitory effect on apoptosis. The role of the c-neu proto-oncogene in normal development is unclear, though its expression is seen in a variety of fetal tissues. We have used homologous recombination and gene targeting strategies to disrupt the c-neu gene to understand its potential role in development. Analysis of several generations of these animals has revealed that the c-neu gene is vital to development. No animals carrying two copies of the mutated gene develop to term. Homozygous mutants do not live past day 10 of gestation.