Experiment
Pbw2 and Alcw2 map to 40 cM on mouse Chromosome 4 and are associated with pentobarbital and alcohol withdrawal severity, respectively. In this study the authors narrowed the QTL interval of Pbw2 and Alcw2 to 1.8 cM using an interval specific congenic strain derived from C57BL/6J donor DNA on a DBA/2J genetic background. The region of C57BL/6J-derived DNA is between D4Mit297 (38 cM) and D4Mit115 (38.7 cM). This interval is syntenic to human Chromosome 9p24-p22.3. Congenic animals display considerably decreased pentobarbital and alcohol withdrawal severity compared to background strain DBA/2J.
The Ensembl, GenBank, and Celera databases were mined for candidate genes located within this 1.8 cM interval. Sixteen genes were identified and one of these, Mpdz, showed differential expression between C57BL/6J and DBA/2J. Mpdz mRNA was more abundant in the brain of parental strain C57BL/6J compared to DBA/2J, and Mpdz protein was found to be elevated in congenic animals compared to DBA/2J.
Association between Mpdz expression and pentobarbital and alcohol withdrawal was analyzed in several inbred strains: C3H/HeJ, C57BL/6J, CBA/J, BALB/cJ, and DBA/2J. The finding was that lower Mpdz expression is associated with greater pentobarbital and alcohol withdrawal seizure susceptibility (P<0.05).
Authors conclude that Mpdz is a quantitative trait gene (QTG) with pleiotropic effects on predisposition to alcohol and barbituate addiction and withdrawal susceptibility.
Analysis Tools