Accession Number : ADA321345

Title :   Mouse Models of the Neu Ligand Interaction with its Receptor in Mammary Gland Tumorigenesis and Development.

Descriptive Note : Annual rept. 1 Jun 95-31 May 96,

Corporate Author : HARVARD COLL CAMBRIDGE MA

Personal Author(s) : Krane, Ian M.

PDF Url : ADA321345

Report Date : JUL 1996

Pagination or Media Count : 28

Abstract : To test if Neu differentiation factor (NDF), an activator of the c-neu gene, is proliferative 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.

Descriptors :   *MODELS, *LIGANDS, *MICE, *RECEPTOR SITES(PHYSIOLOGY), *MAMMARY GLANDS, *BREAST CANCER, ACTIVATION, EPITHELIUM, TISSUES(BIOLOGY), STOCHASTIC PROCESSES, INTERACTIONS, NEOPLASMS, TARGETING, GENES, RECOMBINATION REACTIONS, INHIBITION, ABNORMALITIES, FETUS, LACRIMAL GLANDS.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE