| First Author | Fehr C | Year | 2002 |
| Journal | J Neurosci | Volume | 22 |
| Issue | 9 | Pages | 3730-8 |
| PubMed ID | 11978849 | Mgi Jnum | J:76251 |
| Mgi Id | MGI:2178909 | Doi | 10.1523/JNEUROSCI.22-09-03730.2002 |
| Citation | Fehr C, et al. (2002) Congenic mapping of alcohol and pentobarbital withdrawal liability loci to a <1 centimorgan interval of murine chromosome 4: identification of Mpdz as a candidate gene. J Neurosci 22(9):3730-8 |
| abstractText | Risk for onset of alcoholism is related to genetic differences in acute alcohol withdrawal liability. We previously mapped a locus responsible for 26% of the genetic variance in acute alcohol withdrawal convulsion liability to a >35 centimorgan (cM) interval of murine chromosome 4. Here, we narrow the position of this locus to a <1 cM interval (approximately 1.8 megabase, containing 15 genes and/or predicted genes) using a combination of novel, interval-specific congenic strains and recombinant progeny testing. We report the development of a small-donor-segment congenic strain, which confirms capture of a gene affecting alcohol withdrawal within the <1 cM interval. We also confirm a pentobarbital withdrawal locus within this interval, suggesting that the same gene may influence predisposition to physiological dependence on alcohol and a barbiturate. This congenic strain will be invaluable for determining whether this interval also harbors a gene(s) underlying other quantitative trait loci mapped to chromosome 4, including loci affecting voluntary alcohol consumption, alcohol-induced ataxia, physical dependence after chronic alcohol exposure, and seizure response to pentylenetetrazol or an audiogenic stimulus. To date, Mpdz, which encodes the multiple PSD95/DLG/ZO-1 (PDZ) domain protein (MPDZ), is the only gene within the interval shown to have allelic variants that differ in coding sequence and/or expression. Sequence analysis of 15 standard inbred mouse strains identifies six Mpdz haplotypes that predict three MPDZ protein variants. These analyses, and evidence using interval-specific congenic lines, show that alcohol withdrawal severity is genetically correlated with MPDZ status, indicating that MPDZ variants may influence alcohol withdrawal liability. |
