Comparative inter-strain sequence analysis of the putative regulatory region of murine psychostimulant-regulated gene GNB1 (G protein beta 1 subunit gene).
We isolated a cDNA clone from a murine genomic library of C57BL/6 strain, carrying 13.8 kb of nucleotides including exon 1 of heterotrimeric GTP-binding protein beta 1 subunit gene (genetic symbol, GNB1) and 10.6 kb of the 5' flanking region. Sequence comparison with GNB1 gene locus from 129Sv strain revealed a 0.2% divergence in a 13.2 kb common region between these two strains. The divergence consisted of eight single nucleotide polymorphisms, three insertions and one deletion, with 129Sv used as the reference. The exon 1 and the putative regulation elements, such as cyclic AMP response element, AP1, AP2, Sp1 and nuclear factor-kappa B recognition sites, were perfectly conserved. The expression of GNB1 mRNA was significantly increased in mouse striatum 2 h after single methamphetamine administration with an approximately 150% expression level compared with the basal level. In contrast, no change in the expression level was observed in the cerebral cortex. After the chronic methamphetamine treatment regimen, the expression level of GNB1 mRNA did not change in any brain regions examined. These results suggest (1) that the 5' flanking nucleotide sequence of GNB1 gene was strictly conserved for its possible contribution to the same change in the expression level between the mouse strains in response to psychostimulants and (2) that the initial process of development of behavioral sensitization appeared to occur parallel to the significant increase in the expression level of GNB1 gene in the mouse striatum.
Kitanaka
Nobue
N
Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. kitanaka-hyg@umin.ac.jp
Kitanaka
Junichi
J
Walther
Donna
D
Wang
Xiao-Bing
XB
Uhl
George R
GR
D000818:Animals; D001483:Base Sequence; D003342:Corpus Striatum / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D044387:GTP-Binding Protein beta Subunits; D015870:Gene Expression / Q000187:drug effects*; D015723:Gene Library; D014644:Genetic Variation; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013045:Species Specificity
D017931:DNA Primers; D018076:DNA, Complementary; D044387:GTP-Binding Protein beta Subunits; C491082:Gnb1 protein, mouse; D008694:Methamphetamine; D020962:Heterotrimeric GTP-Binding Proteins