Browsing by Author "Philips, Mari-Anne"

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    Characterization of Myg1 gene and protein: expression patterns, subcellular localization, gene deficient mouse and functional polymorphisms in human
    (2010-05-11T06:59:20Z) Philips, Mari-Anne
    Myg1 is one of the most conserved genes that has been evolutionarily crucial to maintain from protozoans to humans. Despite that Myg1 has not been associated with any remarkable disease conditions or fundamental cellular processes. The main purpose of the current study was to characterize Myg1 (Melanocyte proliferating gene 1) gene and to generate relevant data about this novel gene and protein. In our study group, Myg1 was first identified as a most extensively up-regulated gene in the amygdaloid area of rats after cat odour-induced anxiety (Kõks et al, 2004). Studies linked to the current dissertation were designed to shed light on the function of the Myg1 gene that had previously been cited in only one scientific abstract (Smicun, 2000) describing Myg1 as a highly expressed gene in freely proliferating melanocytes and downregulated in malignant melanoma cells. In the current study we found that in adult tissues Myg1 mRNA expression is ubiquitous and homogeneous; in different embryonic phases Myg1 expression is characterized by a specific pattern and dynamic intensity, indicating developmental impact of Myg1. Myg1 localizes in the nucleus and mitochondria and we also demonstrated the existence of nuclear and mitochondrial targeting signals in the N-terminal region of human and mouse Myg1 proteins. We showed that Myg1 4Gln allele that has remarkable prevalence in the Nigerian population, disturbs mitochondrial entrance of Myg1. Because our subjects from the Estonian population were consistently homozygous for Myg1 4Arg allele, we can not confirm the relevance of Myg1 Arg4Gln, but our current results suggest that Myg1 has indispensable functions in the mitochondria. According to our studies it is most likely that Myg1 is involved in cellular pathways implicated in cellular stress, immune response, development and metabolism. Phenotyping of Myg1-deficient mice revealed that Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1-deficiency caused moderate alterations in anxiety-related behaviour and stress-reactions in mice, but also remarkable reduction of sex-dependent behavioural differences. In our primary screen Myg1-deficient mice displayed no significant alterations in immune response or metabolic activity but several mild tendencies encourage us to study these functions further in Myg1 (-/-) mice. Both MYG1 promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the MYG1 gene. Our in vivo and in vitro promoter activity analysis together with association analysis confirms that -119C/G polymorphism influences MYG1 mRNA levels. Our results suggest that more active -119G is the risk-allele for the development of vitiligo and more specifically risk-allele for the maintenance of the active progression stage of the disease.
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    IgLON valke kodeerivate geenide ekspressiooni muutused skisofreeniapatsientide dorsolateraalses frontaalkoores
    (Tartu Ülikool, 2016) Kaare, Maria; Philips, Mari-Anne; Lilleväli, Kerstin; Tõnissoo, Tambet; Tartu Ülikool. Loodus- ja tehnoloogiateaduskond; Tartu Ülikool. Molekulaar- ja rakubioloogia instituut
    Mitmed uuringud on näidanud, et IgLON perekonna neuraalsed adhesioonimolekulid (OPCML, NTM, LSAMP, NEGR1) on olulisteks kanditaatideks skisofreenia tekke põhjustajatena. IgLONid osalevad neuriitide väljakasvus, sünapsite moodustumises ja nende elimineerimises ja neurogeneesis. On näidatud LSAMP taseme 20% tõusu skisofreenia patsientide postmortaalses dorsolateraalses prefrontaalkoores. Kindlaks on tehtud ka teatud SNPid LSAMP geenis, mis on seotud skisofreenia tekkega. Töö eesmärgiks on iseloomustada IgLON perekonna adhesioonimolekulide ekspressiooni skisofreenia patsientide dorsolateraalses prefrontaalkoores, kasutades selleks qPCR. LSAMP, NTM ja OPCML alternatiivsete promootorite 1a ja 1b aktiivsuseid mõõdeti eraldi. Statistiliselt oluline erinevus skisofreenia patsientide ja kontrollisikute vahel esines NEGR1 (P˂0,001) ja NTM 1b (P˂0,01) puhul. Seega võivad muutused IgLON perekonna adhesioonimolekulide ekspressioonis olla üheks skisofreenia tekkepõhjuseks.