Shar Pei dogs – a model for hereditary periodic fevers and amyloidosis
✍ Scribed by M. Olsson; K. Truvé; G.R. Pielberg; L. Andersson; Å. Hedhammar; K. Lindblad-Toh
- Book ID
- 103851021
- Publisher
- Elsevier
- Year
- 2010
- Tongue
- English
- Weight
- 74 KB
- Volume
- 27
- Category
- Article
- ISSN
- 1871-6784
No coin nor oath required. For personal study only.
✦ Synopsis
genetically modified mice lacking the noradrenaline transporter (NET-KO) [2] display "depressive-resistant" behavior. They showed significantly shorter immobility time in both forced swim test and tail suspension test [1]. The present study was designed to examine genomic differences between NET-KO mice and wild type (WT) mice. Additional grup of WT mice was administered with desipramine (DMI). To achieve this goal the whole genome Affymetrix microarray was used.
We injected group of wild type mice by desipramine (i.p.; 20 mg/kg), once daily for seven consecutive days. Group of WT mice and NET-KO mice were injected 0.9% physiological saline. The brains were frozen, RNA was extracted from frontal cortex. Biotinylated cRNA were prepared according to the protocol and hybridized to Affymetrix microarray. Data was analyzed using ChipInspector 2.1 (Genomatix). Comparisons between knock-out, WT or WT group after DMI injection were performed by statistic algorithm of ChipInspector (FDR 0%).
We selected statistically significant group of 92 transcript (27 genes) after comparison of NET-KO and WT mice and 88 transcripts (18 genes) after comparison of group of WT mice following DMI administration. Both groups of genes were analyzed using BiblioSphere Pathway Edition (Genomatix). Some of them were connected in relation network according to literature and biological filter. Genes like Slc6a2, Fos, Ang, Arc, Paip1, Gadd45gip1, Nr4a1, Prdx2, Ier5 differentiate NET-KO from WT mice and they are involved in regulation of macromolecule biosynthetic process, regulation of gene expression and cellular metabolic processes. Genes like Spnb2, Mef2c, Ncam1, Hsp90ab1, Kif1b, Ddx6, Gsk3b differentiate mice after DMI injected from WT and they are involved in organ morphogenesis, positive regulation of biological process, cell communication and transport. Most interesting finding is the upregulation of expression of Slc6a2 in NET-KO comparisons to wild type mice. We validated these data by RT-PCR and we observed significant increase in expression of different parts of this gene. All of statistically significant genes will be verified by RT-PCR in selected structures of the brain.
It may be concluded that recently developed microarray technique adopted to the study of genetically modified mice lacking the noradrenaline transporter allowed to find an interesting group of genes which could be involved in the mechanism of action of antidepressant drugs.