| First Author | Radcliffe RA | Year | 2000 |
| Journal | Alcohol Clin Exp Res | Volume | 24 |
| Issue | 9 | Pages | 1335-42 |
| PubMed ID | 11003198 | Mgi Jnum | J:66631 |
| Mgi Id | MGI:1928781 | Citation | Radcliffe RA, et al. (2000) Mapping of quantitative trait loci for hypnotic sensitivity to ethanol in crosses derived from the C57BL/6 and DBA/2 mouse strains. Alcohol Clin Exp Res 24(9):1335-42 |
| abstractText | BACKGROUND: Acute ethanol sensitivity is thought to be a predisposing factor toward the development of alcoholism. Accumulated evidence suggests that this characteristic may be at least partly heritable. A widely accepted approach for identifying genes thought to contribute to alcoholism is to map quantitative trait loci (QTLs) for various ethanol-related behaviors in rodent models. METHODS: Ethanol sensitivity QTLs were interval-mapped in a C57BL/6 (B6) X DBA/2 (D2) F2 intercross that contained 391 mice. Sensitivity was measured as the duration of loss of righting reflex (LORR) after 4.1 g/kg ip. LORR also was evaluated in a chromosome 1 marker-assisted congenic strain that had an approximately 30 centiMorgan (cM) portion of D2 DNA from the distal end of chromosome 1 introgressed onto a B6 background. RESULTS: A suggestive QTL was mapped on chromosome 1 (LOD = 3.3; approximately 80 cM) and a provisional QTL on chromosome 5 (LOD = 2.3; approximately 26 cM). The provisional chromosome 5 QTL was found to be sex-specific (LOD = 2.5 for males; LOD < 1 for females) with the D2 allele increasing LORR. The chromosome 1 D2 allele decreased LORR. Consistent with the F2 QTL mapping, congenic mice heterozygous for the chromosome 1 interval (B6/D2) had a significantly different mean (+/- SEM) LORR of 74.0 +/- 4.9 min (n = 36) compared with 90.8 +/- 6.2 min (n = 33) for their homozygous (B6/B6) littermates (p = 0.02). Blood ethanol concentration at regain of righting reflex was 377 +/- 10 mg% for the B6/D2 and 368 +/- 10 mg% (p = NS) for the B6/B6. CONCLUSIONS: LORR results in the chromosome 1 congenic mice were consistent with and very similar to what was predicted from the QTL analysis in the B6 X D2 F2 population. These results support a suggestive LORR QTL on the distal end of mouse chromosome 1. The results also indicate that there is a provisional sex-specific LORR QTL on chromosome 5. |
