Transcription profiling of mouse mammary gland of Brca and p53 mutants to identifu Brca1 regulated X-linked genes

We compared the expression levels of X-linked genes in the mammary glands of Brca111/11p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle: virgin, pregnant day 16.5, and lactation day 1, using a cDNA microarray. In about 690 X-linked genes that are expressed at these three stages of mammary cycle of development, we found 16 X-linked genes showed altered expression levels in Brca111/11p53+/- mammary glands in comparison with controls at all three time points. Among them, 9 genes were up-regulated and 7 were down-regulated. This result indicates that mutation of Brca1 could affect expression of a few X-linked genes in mammary tissues. However, this was unlikely caused by failure of X chromosome inactivation, as seven of them were down-regulated, and Xist RNA was expressed in all the Brca1 mutant mammary tissues. Experiment Overall Design: Mutations in breast cancer associated gene-1 (BRCA1) are associated with hereditary breast and ovarian cancers. BRCA1 encodes a tumor suppressor protein that functions in DNA repair, transcriptional regulation, chromatin remodeling, centrosome duplication and checkpoint control, etc.. We were interested in fishing out the genes regulated by Brca1. Three pairs of mammary glands from Brca111/11p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle were analyzed by microarray for gene expression levels.