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Pregled bibliografske jedinice broj: 428163

Gene expression profiling of cerebellar tissue of ganglioside deficient mice


Mlinac, Kristina; Režen, Tadeja; Heffer, Marija; Rozman, Damjana, Kalanj Bognar, Svjetlana
Gene expression profiling of cerebellar tissue of ganglioside deficient mice // The third Croatian Congress of Neuroscience Abstract Book / Croatian Society for Neuroscience and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia (ur.).
Zagreb: School of Medicine, University of Zagreb, Croatian Institute for Brain Research, 2009. str. 63-64 (poster, domaća recenzija, sažetak, znanstveni)


Naslov
Gene expression profiling of cerebellar tissue of ganglioside deficient mice

Autori
Mlinac, Kristina ; Režen, Tadeja ; Heffer, Marija ; Rozman, Damjana, Kalanj Bognar, Svjetlana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The third Croatian Congress of Neuroscience Abstract Book / Croatian Society for Neuroscience and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia - Zagreb : School of Medicine, University of Zagreb, Croatian Institute for Brain Research, 2009, 63-64

Skup
The Third Croatian Congress of Neuroscience

Mjesto i datum
Zadar, Hrvatska, 24-26.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Gangliosides; gene expression

Sažetak
Gangliosides, glycosphingolipids containing sialic acids, are localized in the outer leaflet of the plasma membranes. Together with cholesterol, gangliosides are organized in specialized membrane microdomains (lipid rafts) involved in membrane-associated events such as cell-cell interaction, adhesion, cell differentiation, growth control and receptor functions. Greatest variety and amount of ganglioside structures have been found in brain tissue. Gangliosides are involved in brain development and maturation ; on the other hand, deficiency of ganglioside synthesis leads to degeneration and altered axon-glial interactions in central nervous system. In this study we analyzed the differences between transcriptomes of GD3 synthase (Siat8a) knockout (KO) and wild type (wt) mice. Siat8a knockout mice lack disialylated b-series ganglioside structures (GD3, GD2, GD1b, GT1b). Upon aging, these mice show dysmyelination and impaired nerve regeneration. GT1b ganglioside is a ligand for myelin-associated glycoprotein (MAG) and mutations in the human ortholog of Siat8a gene (ST8SIA1) have recently been linked with the risk of developing multiple sclerosis. RNA was isolated from brain samples of 3 wt and 3 KO animals. After quantitative and qualitative analysis of the RNA, cerebellar samples were labeled for two color microarray experiments. Samples were hybridized to Agilent's 1x22K Whole Mouse Genome Oligo Microarrays (6 arrays total) and analyzed with GenePix Pro and BRB-Assay Tools. Gene annotation was performed using publicly available annotation tools – GeneCoDis2 and DAVID Bioinformatics Database Gene ID Conversion Tool. After extensive analysis (and consideration of feature exclusion criteria) a list of differentially expressed genes was retrieved. The gene found to be most upregulated was Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) involved in Ras signaling pathway ; one of the most downregulated genes found was Mapkapk2 (MAP kinase-activated protein kinase 2). In the biological process ontology the most frequent annotation term was signal transduction. Preliminary results indicate that the majority of differentially expressed genes in the cerebellum of GD3 synthase deficient mice are involved in the signal transduction. In order to confirm these results, the expression of individual genes needs to be determined. We find the results very interesting, having in mind that normal cerebellar tissue is particularly enriched in b-series gangliosides and that in vitro studies showed gangliosides to be implicated in Ras signaling pathway. Our results show for the first time in animal model that deficient synthesis of GD3 and consequently other b-series gangliosides, beside effects on membrane lipid homeostasis, is also probably associated to alterations in complex signaling pathways.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
Oralna prezentacija



POVEZANOST RADA


Projekt / tema
108-1081870-1877 - Uloga membranskih lipida u moždanom razvitku, starenju i neurodegeneraciji (Svjetlana Kalanj-Bognar, )

Ustanove
Medicinski fakultet, Zagreb