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

Z. K. Mirnics, Karoly Mirnics, D. Terrano, D. A. Lewis, S. S. Sisodia, N. F. Schor

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 coregulated transcript network; some of the genes participating in this expression network may contribute to the pathophysiology of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)863-878
Number of pages16
JournalMolecular Psychiatry
Volume8
Issue number10
DOIs
StatePublished - Nov 11 2003

Fingerprint

Presenilin-1
DNA Fingerprinting
Oligonucleotide Array Sequence Analysis
Brain
Blood Vessels
Alzheimer Disease
mouse presenilin 1
Lipid Metabolism
Nervous System
Embryonic Development
Extracellular Matrix
Embryonic Structures
Gene Expression
Mutation

Keywords

  • Alzheimer's disease
  • Knockout
  • Lipid metabolism
  • Notch signaling
  • Oligonucleotide GeneChips
  • Presenilin
  • Transcript network
  • in situ hybridization

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes. / Mirnics, Z. K.; Mirnics, Karoly; Terrano, D.; Lewis, D. A.; Sisodia, S. S.; Schor, N. F.

In: Molecular Psychiatry, Vol. 8, No. 10, 11.11.2003, p. 863-878.

Research output: Contribution to journalArticle

Mirnics, Z. K. ; Mirnics, Karoly ; Terrano, D. ; Lewis, D. A. ; Sisodia, S. S. ; Schor, N. F. / DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes. In: Molecular Psychiatry. 2003 ; Vol. 8, No. 10. pp. 863-878.
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