Presenilin-1-dependent transcriptome changes

K. Mirnics, Z. Korade, Dominique Arion, Orly Lazarov, Travis Unger, Melissa Macioce, Michael Sabatini, David Terrano, Katherine C. Douglass, Nina F. Schor, Sangram S. Sisodia

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Familial forms of Alzheimer's disease (FADs) are caused by the expression of mutant presenilin 1 (PS1) or presenilin 2. Using DNA microarrays, we explored the brain transcription profiles of mice with conditional knock-out of PS1 (cKO PS1) in the forebrain. In parallel, we performed a transcription profiling of the hippocampus and frontal cortex of the FAD-linked ΔE9 mutant transgenic (TG) mice and matched controls [TG mice expressing wild-type human PS1 (hPS1)]. When the TG and cKO datasets were cross-compared, the majority of the 30 common expression alterations were in opposite direction, suggesting that the FAD-linked PS1 variant produces transcriptome changes primarily by gain of aberrant function. Our microarray studies also revealed an unanticipated inverse correlation of transcript levels between the brains of mice that coexpress ΔE9 hPS1+ amyloid precursor protein (APP)695 Swe and ΔE9 hPS1 single transgenic mice. The opposite directionality of these changes in transcript levels must be a function of APP and/or APP derivatives.

Original languageEnglish
Pages (from-to)1571-1578
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number6
DOIs
Publication statusPublished - Feb 9 2005

Fingerprint

Presenilin-1
Amyloid beta-Protein Precursor
Transcriptome
Transgenic Mice
Alzheimer Disease
Presenilin-2
Brain
Frontal Lobe
Prosencephalon
Oligonucleotide Array Sequence Analysis
Hippocampus

Keywords

  • Alzheimer's disease
  • Animal model
  • DNA microarray
  • Gene expression
  • Presenilin
  • Transcriptome

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mirnics, K., Korade, Z., Arion, D., Lazarov, O., Unger, T., Macioce, M., ... Sisodia, S. S. (2005). Presenilin-1-dependent transcriptome changes. Journal of Neuroscience, 25(6), 1571-1578. https://doi.org/10.1523/JNEUROSCI.4145-04.2005

Presenilin-1-dependent transcriptome changes. / Mirnics, K.; Korade, Z.; Arion, Dominique; Lazarov, Orly; Unger, Travis; Macioce, Melissa; Sabatini, Michael; Terrano, David; Douglass, Katherine C.; Schor, Nina F.; Sisodia, Sangram S.

In: Journal of Neuroscience, Vol. 25, No. 6, 09.02.2005, p. 1571-1578.

Research output: Contribution to journalArticle

Mirnics, K, Korade, Z, Arion, D, Lazarov, O, Unger, T, Macioce, M, Sabatini, M, Terrano, D, Douglass, KC, Schor, NF & Sisodia, SS 2005, 'Presenilin-1-dependent transcriptome changes', Journal of Neuroscience, vol. 25, no. 6, pp. 1571-1578. https://doi.org/10.1523/JNEUROSCI.4145-04.2005
Mirnics, K. ; Korade, Z. ; Arion, Dominique ; Lazarov, Orly ; Unger, Travis ; Macioce, Melissa ; Sabatini, Michael ; Terrano, David ; Douglass, Katherine C. ; Schor, Nina F. ; Sisodia, Sangram S. / Presenilin-1-dependent transcriptome changes. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 6. pp. 1571-1578.
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