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Gene expression profiling of mammary epithelial cells isolated from Cuzd1-null and heterozygous mice on day 18 of pregnancy

ABSTRACT: Our study revealed that CUZD1 (CUB and zona pellucida-like domain containing protein-1) is a novel target of estrogen regulation in the mouse mammary epithelium. Mice lacking Cuzd1 exhibit delayed ductal outgrowth during puberty and a striking impairment in ductal branching and alveolar development during pregnancy. Ablation of Cuzd1 led to a marked reduction in steroid-induced proliferation of mammary ductal and alveolar epithelium. To identify the downstream targets of Cuzd1 in mammary gland development, we performed gene expression profling of mammary epithlial cells isolated from Cuzd1-null and its heterozygous litteremates on day 18 of pregnancy. The microarray results revealed downregulation of mRNAs corresponding to several members of the epidermal growth factor family in mammary epithelial cells of Cuzd1-null mice. Consequently, the activation of the ERBB receptors, ERBB1 and ERBB4, and their downstream target STAT5, was disrupted in Cuzd1-null mammary tissue. Collectively, these findings support a unique role for CUZD1 as a critical mediator of the steroid-induced proliferation and differentiation of ductal epithelium during pregnancy and lactation. To investigate the functional role of Cuzd1, we created Cuzd1-null mice by homologous recombination using mouse embryonic stem cells. As severe defect was observed in alveolargenesis and lactation of Cuzd1 null mammary gland, we purified mammary epithlial cells from day18 pregnant mice (n=5 for each genotype), purified total RNA from these cells, pooled these samples and then hybridized to high density affymetrix microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Quanxi Li

PROVIDER: E-GEOD-30939 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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