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Published on: May 12, 2015
DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes
Z K Mirnics1, K Mirnics, D Terrano
1Department of Pediatrics and Neurology, University of Pittsburgh, School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA. zkorade@pitt.edu
Molecular Psychiatry
|September 30, 2003
Summary
Presenilin 1 (PS1) is crucial for brain development and its deficiency impacts neural and vascular growth. This study reveals PS1 influences key gene networks involved in brain development and potentially Alzheimer's disease.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Presenilin 1 (PS1) is vital for nervous system development.
- PS1 mutations are linked to familial Alzheimer's disease.
- PS1 deficiency in mice causes developmental defects and embryonic lethality.
Purpose of the Study:
- To identify transcript networks regulated by Presenilin 1 in the developing brain.
- To understand the role of PS1 in neural and vascular development.
Main Methods:
- Analysis of PS1-deficient and control mouse brains at embryonic days E12.5 and E14.5.
- Utilized Affymetrix MG_U74Av2 oligonucleotide microarrays for gene expression profiling.
Main Results:
- Overall molecular brain development appeared similar between PS1-deficient and control embryos.
- Significant differences in gene expression were observed in PS1-deficient brains, affecting neural differentiation, extracellular matrix, vascular development, Notch signaling, and lipid metabolism.
- Some transcript alterations were stage-specific (E12.5 or E14.5), while others were consistent across both stages.
Conclusions:
- PS1 influences a co-regulated transcript network essential for brain development.
- Dysregulation of these PS1-dependent genes may contribute to Alzheimer's disease pathophysiology.
- PS1 plays a broader role in developmental processes than previously understood.
