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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
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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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 külföldön készült közlemény
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
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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