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Publication : DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes.

First Author  Mirnics ZK Year  2003
Journal  Mol Psychiatry Volume  8
Issue  10 Pages  863-78
PubMed ID  14515137 Mgi Jnum  J:85858
Mgi Id  MGI:2677173 Doi  10.1038/sj.mp.4001389
Citation  Mirnics ZK, et al. (2003) DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes. Mol Psychiatry 8(10):863-78
abstractText  Presenilin 1 (PS1) plays a critical role in the nervous system development and PS1 mutations have been associated with familial Alzheimer's disease. PS1-deficient mice exhibit alterations in neural and vascular development and die in late embryogenesis. The present study was aimed at uncovering transcript networks that depend on intact PS1 function in the developing brain. To achieve this, we analyzed the brains of PS1-deficient and control animals at embryonic ages E12.5 and E14.5 using MG_U74Av2 oligonucleotide microarrays by Affymetrix. Based on the microarray data, overall molecular brain development appeared to be comparable between the E12.5 and E14.5 PS1-deficient and control embryos. However, in brains of PS1-deficient mice, we observed significant differences in the expression of genes encoding molecules that are associated with neural differentiation, extracellular matrix, vascular development, Notch-related signaling and lipid metabolism. Many of the expression differences between wild-type and PS1-deficient animals were present at both E12.5 and E14.5, whereas other transcript alterations were characteristic of only one developmental stage. The results suggest that the role of PS1 in development includes influences on a highly co-regulated transcript network; some of the genes participating in this expression network may contribute to the pathophysiology of Alzheimer's disease.Molecular Psychiatry (2003) 8, 863-878. doi:10.1038/sj.mp.4001389
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