Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Analysis of mRNA expression differences in the skin of Casp-8F/–K5-Cre and Casp-8F/+K5-Cre mice

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE17344: Analysis of spatial mRNA expression differences in the skin of Casp-8F/–K5-Cre or Casp-8F/+K5-Cre mice GSE17345: Analysis of temporal mRNA expression changes in cultured keratinocytes from Casp-8F/–K5-Cre and Casp-8F/+K5-Cre mice Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Oliver Dittrich-Breiholz

PROVIDER: E-GEOD-17365 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease.

Kovalenko Andrew A Kim Jin-Chul JC Kang Tae-Bong TB Rajput Akhil A Bogdanov Konstantin K Dittrich-Breiholz Oliver O Kracht Michael M Brenner Ori O Wallach David D

The Journal of experimental medicine 20090831 10

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor kappaB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase ...[more]

PMID: 19720838

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Project description:Injury of the CA1 subregion induced by a single injection of kainic acid (1M-CM-^WKA) is attenuated when juvenile animals (P20) have a history of two sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early life conditioning seizures, we profiled and compared the transcriptomes of CA1 subregions from control, 1M-CM-^WKA, and 3M-CM-^WKA treated animals. More genes were regulated following 3M-CM-^WKA (9.6%) than after 1M-CM-^WKA (7.1%). Following 1M-CM-^WKA, genes supporting oxidative stress, growth, development, inflammation, and neurotransmission were upregulated (e.g., Cacng1, Nadsyn1, Kcng1, Aven, S100a4, GFAP, Vim, Hrsp12, Grik1). After 3M-CM-^WKA, protective genes were differentially over-expressed (e.g., Cat, Gpx7, GAD1, Hspa12A, Foxn1, adenosine A1 receptor, Ca2+ adaptor and homeostatic proteins, Cacnb4, Atp2b2, anti-apoptotic Bcl-2 gene members, intracellular trafficking protein, Grasp, suppressor of cytokine signaling (Socs3)). Distinct anti-inflammatory interleukins not observed in adult tissues (e.g., IL6 transducer, IL23 and IL33 or their receptors (ILF2)) were also over-expressed. Several transcripts were validated by real-time polymerase chain reaction (QPCR) and immunohistochemistry. QPCR showed that casp 6 was increased after 1M-CM-^WKA but reduced after 3M-CM-^WKA; pro-inflammatory gene cox1 was either upregulated or unchanged after 1M-CM-^WKA but reduced by ~70% after 3M-CM-^WKA. Enhanced GFAP immunostaining following 1M-CM-^WKA was selectively attenuated in the CA1 subregion after 3M-CM-^WKA. The observed differential transcriptional responses may contribute to early life seizure-induced pre-conditioning and neuroprotection by reducing glutamate receptor-mediated Ca2+ permeability of the hippocampus and redirecting inflammatory and apoptotic pathways which could lead to new genetic therapies for epilepsy. The transcriptomes of the hippocampal CA1 region of Sprague Dawley 23-day-old male rats after 1 or 3 seizures induced by kainic acid injection were compared to the corresponding controls (injected with PBS) using Duke 27k oligonucleotide arrays.

Dataset Information

Analysis of mRNA expression differences in the skin of Casp-8F/–K5-Cre and Casp-8F/+K5-Cre mice

Publications

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease.

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