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  • Original Research Article
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DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes

Abstract

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.

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Acknowledgements

We thank Dr Pat Levitt for useful comments on the experimental design and manuscript, as well as Ms Deborah Hollingshead for the skillful microarray hybridizations. This work is supported by CHP Research Advisory Committee and Child Neurology Training Grant NS07495-01A1 and PIND Grant (ZKM), Carol Ann Craumer Endowment of CHP (NFS), 2002 NARSAD Young Investigator Award (KM) and Ellison Medical Foundation Senior Scholar Award (SSS) and The Fidelity Foundation (SSS).

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Mirnics, Z., Mirnics, K., Terrano, D. et al. DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes. Mol Psychiatry 8, 863–878 (2003). https://doi.org/10.1038/sj.mp.4001389

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