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001-es BibID:BIBFORM039779
Első szerző:Saito, Mariko
Cím:Mouse striatal transcriptome analysis : effects of oral self-administration of alcohol / Saito Mariko, Szakall Istvan, Toth Reka, Kovacs Krisztina M., Oros Melinda, Prasad Vidudala V. T. S., Blumenberg Miroslav, Vadasz Csaba
Dátum:2004
ISSN:0741-8329
Megjegyzések:Results of recent studies support the notion that substance self-administration is partially a genetically controlled component of addiction tied to habit formation and cellular modification of the striatum. Aiming to define pathways among genomic, neural, and behavioral determinants of addiction, we investigated global striatal gene expression in a paradigm of oral self-administration of alcohol by using genomically very similar alcohol-nonpreferring B6.Cb(5)i(7)-alpha 3/Vad (C5A3) and alcohol-preferring B6.Ib(5)i(7)-beta 25A/Vad (I5B25A) quasi-congenic mouse strains and their progenitors, C57BL/6By (B6By) and BALB/cJ. Expression of 12,488 genes and expressed sequence tags (ESTs) was studied by using 24 high-density oligonucleotide microarrays. Transcript signal intensity differences were analyzed with z test after iterative median normalization across groups and Hochberg step-down Bonferroni procedure. As expected, striatal transcriptome differences were far more extensive between the independently derived progenitor strains than between the quasi-congenic strains and their background partner, B6By. However, the genes, which were differentially expressed between the quasi-congenic strains and their background partner, were not subsets of the progenitorial differences and were not located on the chromosome segments introgressed into the quasi-congenic strains from the donor BALB/cJ strain that have been so far defined. Although 25 transcripts showed significantly different expression between the progenitor strains, only two transcripts, phosphatidylserine decarboxylase and a hypothetical 21.2-kDa protein, and one transcript, molybdenum co-factor synthesis 2, showed significantly different expression between C5A3 and I5B25A, and between B6By and I5B25A, respectively. The latter three transcripts are not located on previously identified chromosome segments introgressed from the donor BALB/cJ strain, supporting the suggestion of trans-acting regulatory variations among strains. Exposure to alcohol did not induce statistically significant striatal gene expression changes in any of the mouse strains. In conclusion, the results support the hypothesis that in functional genomic studies the chance of detecting function-relevant genes can be increased by the comparative analysis of quasi-congenic and background strains because the number of functionally irrelevant, differentially expressed genes between genomically similar strains is reduced. Lack of statistically significant alcohol-induced changes in transcript abundance indicated that oral self-administration had subtle effects on striatal gene expression and directed attention to important implications for the experimental design of future microarray gene expression studies on complex behaviors.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Alcohol. - 32 : 3 (2004), p. 223-241. -
További szerzők:Szakáll István Tóth Réka Kovács Krisztina M. Oros Melinda (1975-) (molekuláris biológus) Prasad, Vidudala V. T. S. Blumenberg, Miroslav Vadász Csaba
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2.

001-es BibID:BIBFORM039715
035-os BibID:PMID:12657375
Első szerző:Saito, Mariko
Cím:Variants of kappa-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice / Mariko Saito, Marissa A. Ehringer, Reka Toth, Melinda Oros, István Szakall, James M. Sikela, Csaba Vadasz
Dátum:2003
ISSN:0741-8329
Megjegyzések:Results of recent studies have indicated an association between voluntary alcohol intake and activities of kappa-opioid receptor systems in animal models. We assessed the possibility that genetic differences observed in alcohol preference among mouse strains are related to possible polymorphisms of the kappa-opioid receptor gene (Oprk1). We compared DNA sequences of the coding region and the promoter/regulatory region of Oprk1 among C57BL/6ByJ (B6, alcohol-preferring), BALB/cJ (alcohol-avoiding), CXBI (alcohol-avoiding), and six B6.C and B6.I Recombinant QTL Introgression (RQI) strains, which carry approximately 3% of the donor BALB/cJ genome in the background B6 genome and showed various alcohol preferences. Although there were no sequence differences in the coding region, BALB/cJ had a single nucleotide polymorphism (SNP) in the promoter region, which was not detected in other strains. The results indicate that the difference in alcohol preference between B6 and BALB/cJ is not correlated with polymorphisms of Oprk1. However, results of further studies comparing Oprk1 mRNA expression between B6 and BALB/cJ showed that Oprk1 expression is regulated differently in these strains. Also, DBA/2J mice (alcohol-avoiding) showed expression of Oprk1 mRNA subtypes (alternatively spliced) different from B6 and BALB/cJ mice. Search of the Celera Genomics database indicated that DBA/2J had several SNP sites in the promoter/regulatory regions, which might explain the different expression of Oprk1 mRNA subtypes in this strain. The strain-dependent variation in the expression of alternatively spliced genes can be a significant source of phenotypic variation of complex traits such as alcohol preference.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Alcohol. - 29 : 1 (2003), p. 39-49. -
További szerzők:Ehringer, Marissa A. Tóth Réka Oros Melinda (1975-) (molekuláris biológus) Szakáll István Sikela, James M. Vadász Csaba
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3.

001-es BibID:BIBFORM047535
Első szerző:Vadász Csaba
Cím:Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking? / Csaba Vadasz, Mariko Saito, Beatrix M. Gyetvai, Melinda Oros, Istvan Szakall, Krisztina M. Kovacs, Vidudala V. T. S. Prasad, Reka Toth
Dátum:2007
ISSN:0888-7543
Megjegyzések:Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development and symptoms, such as craving, loss of control, physical dependence, and tolerance, have been linked to changes in mesolimbic, mesocortical neurotransmitter systems utilizing biogenic amines, GABA, and glutamate. Identification of genes predisposing to alcoholism, or to alcohol-related behaviors in animal models, has been elusive because of variable interactions of multiple genes with relatively small individual effect size and sensitivity of the predisposing genotype to lifestyle and environmental factors. Here, using near-isogenic advanced animal models with reduced genetic background interactions, we integrate gene mapping and gene mRNA expression data in segregating and congenic mice and identify glutamate receptor metabotropic 7 (Grm7) as a cis-regulated gene for alcohol consumption. Traditionally, the mesoaccumbal dopamine reward hypothesis of addiction and the role of the ionotropic glutamate receptors have been emphasized. Our results lend support to an emerging direction of research on the role of metabotropic glutamate receptors in alcoholism and drug addiction. These data suggest for the first time that Grm7 is a risk factor for alcohol drinking and a new target in addiction therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Genomics. - 90 : 6 (2007), p. 690-702. -
További szerzők:Saito, Mariko Gyetvai Beatrix Oros Melinda (1975-) (molekuláris biológus) Szakáll István Kovács Krisztina M. Prasad, Vidudala V. T. S. Tóth Réka
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4.

001-es BibID:BIBFORM039786
Első szerző:Vadász Csaba
Cím:Mesencephalic dopamine neuron number and tyrosine hydroxylase content: Genetic control and candidate genes / Vadasz, C., Smiley, J. F., Figarsky, K., Saito, M., Toth, R., Gyetvai, B. M., Oros, M., Kovacs, K. K., Mohan, P., Wang, R.
Dátum:2007
ISSN:0306-4522
Megjegyzések:The mesotelencephalic dopamine system shows substantial genetic variation which fundamentally affects normal and pathological behaviors related to motor function, motivation, and learning. Our earlier radioenzyme assay studies demonstrated significantly higher activity of tyrosine hydroxylase (TH), the first and rate limiting enzyme in the biosynthesis of catecholamine neurotransmitters, in the substantia nigra-ventral tegmental area of BALB/cJ mice in comparison with that of C57BL/6ByJ mice. Here, using quantitative immunoblotting and immunocytochemistry, we tested the hypothesis that mesencephalic TH protein content and number of nigral TH-positive neurons show strain-dependent differences in C57BL/6ByJ and BALB/cJ parallel to those observed in the TH activity studies. Immunoblotting experiments detected significantly higher mesencephalic TH protein content in BALB/cJ in comparison to C57BL/6ByJ (P<0.05). Immunocytochemical studies demonstrated that the number of TH-positive cells in substantia nigra was 31.3% higher in BALB/cJ than that in C57BL/6ByJ (P<0.01), while the average dopamine neuron volume was not significantly different. In a search for candidate genes that modulate TH content and the size of mesencephalic dopamine neuron populations we also studied near-isogenic mouse sublines derived from the C57BL/6ByJ and BALB/cJ progenitor strains. A whole-genome scan with 768 single nucleotide polymorphism markers indicated that two sublines, C4A6/N and C4A6/B, were genetically very similar (98.3%). We found significantly higher mesencephalic TH protein content in C4A6/B in comparison to C4A6/N (P=0.01), and a tendency for higher number of dopamine neurons in the substantia nigra in C4A6/B in comparison to C4A6/N, which, however, did not reach statistical significance. To identify the genetic source of the TH content difference we analyzed the single nucleotide polymorphism (SNP) genotype data of the whole-genome scan, and detected two small differential chromosome segments on chr. 13 and chr. 14. Microarray gene expression studies and bioinformatic analysis of the two differential regions implicated two cis-regulated genes (Spock1 and Cxcl14, chr. 13), and two growth factor genes [bone morphogenetic protein 6 (Bmp6) (chr. 13), and fibroblast growth factor 14 (Fgf14) (chr. 14)]. Taken together, the results suggest that (1) nigral dopamine neuron number and TH protein content may be genetically associated but further studies are needed to establish unequivocally this linkage, and (2) Spock1, Cxcl14, Bmp6, and Fgf14 are novel candidates for modulating the expression and maintenance of TH content in mesencephalic dopamine neurons in vivo.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Neuroscience. - 149 : 3 (2007), p. 561-572. -
További szerzők:Smiley, John Figarsky, K. Saito, Mariko Tóth Réka Gyetvai Beatrix Oros Melinda (1975-) (molekuláris biológus) Kovács, K. K. Mohan, Puneet Wang, Rui
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5.

001-es BibID:BIBFORM039712
035-os BibID:PMID:17273929
Első szerző:Vadász Csaba
Cím:Mapping of QTLs for oral alcohol self-administration in B6.C and B6.I quasi-congenic RQI strains / Csaba Vadasz, Mariko Saito, Beatrix Gyetvai, Melinda Oros, Istvan Szakall, Krisztina M. Kovacs, Vidudala V. T. S. Prasad, Grant Morahan, Reka Toth
Dátum:2007
ISSN:0364-3190
Megjegyzések:One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle-choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (Vadasz et al. (2000) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22:25-34) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12, while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Neurochemical Research. - 32 : 7 (2007), p. 1099-1112. -
További szerzők:Saito, Mariko Gyetvai Beatrix Oros Melinda (1975-) (molekuláris biológus) Szakáll István Kovács Krisztina M. Prasad, Vidudala V. T. S. Morahan, Grant Tóth Réka
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