Transcriptome differences between the frontal cortex and hippocampus of wild-type and humanized presenilin-1 transgenic mice.
OBJECTIVE
The authors investigated the differences between the frontal cortical (Fc) and hippocampal (Hc) transcriptomes of wild type (wt mPS1), humanized presenilin-1 (PS1 [wt hPS1]) and Alzheimer-disease (AD)-linked DeltaE9 hPS1 mutant mice.


METHODS
Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and DeltaE9 hPS1 mutant mice. Whereas these studies analyzed the commonalities of gene expression patterns and commonly-regulated genes across the two brain areas and across the animal models, the current study focused on the gene-expression differences across Fc and Hc, two critical AD-affected brain regions.


RESULTS
The data revealed that in the wild-type mice, there are significant transcriptome differences between the Fc and the Hc tissue, and these expression differences are maintained in humanized transgenic mice carrying the wt hPS1 gene or DeltaE9 hPS1 mutation. Also, they provide evidence that a subset of genes show disturbed regional Fc-Hc gene-expression ratios in the transgenic mice carrying the DeltaE9 hPS1 mutation. Some of these genes, including stearoyl-Coenzyme A desaturase-2 (Scd2) and Prostaglandin D2 synthase (Ptgds), have been previously implicated in the pathology of AD.


CONCLUSIONS
Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology.
Unger
Travis
T
Department of Psychiatry, University of Pittsburgh School of Medicine, E1453 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Korade
Zeljka
Z
Lazarov
Orly
O
Terrano
David
D
Schor
Nina F
NF
Sisodia
Sangram S
SS
Mirnics
Károly
K
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D030541:Databases, Genetic; D005625:Frontal Lobe / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation / Q000235:genetics; D053764:Presenilin-1; D017422:Sequence Analysis, DNA
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1