Quantitative Trait Loci Affecting Initial Sensitivity and Acute Functional Tolerance to Ethanol-Induced Ataxia and Brain cAMP Signaling in BXD Recombinant Inbred Mice
作者： Shelli L. Kirstein , Kirsten L. Davidson , Marissa A. Ehringer , James M. Sikela , V. Gene Erwin
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摘要: In previous work, we identified genetic correlations between cAMP accumulation in the cerebellum and sensitivity to incoordinating effects of ethanol. A correlation suggests that common genes underlie phenotypes investigated. One method for provisionally identifying involved a given phenotypic measure is quantitative trait locus (QTL) analysis. Using panel 30 BXD recombinant inbred strains mice progenitors (DBA/2J C57BL/6J), dowel test ataxia, measured blood ethanol concentrations at time an animal first fell from acute functional tolerance (AFT), investigated signaling cerebellum. Cyclic AMP was whole-cell preparations cerebellar minces individual under basal or stimulated conditions. We conducted genome-wide QTL analysis behavioral biochemical measures with >2000 markers identify significant associations. Western blot comparative sequencing were used compare response element binding protein (CREB) levels protein-coding sequence, respectively. analyses correlating strain means allelic status several associations ( p < 0.01). Analysis variance revealed effect on measures. There initial 6 provisional QTLs four chromosomes, AFT 11 nine chromosomes. Two loci found overlap signaling. Given accumulation, candidate chromosome 1. Comparative sequence performed, compared C57 DBA Creb1 . No differences detected coding CREB. These results suggest although are determined by multiple genes, they may share certain codetermination.
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