Lore3^LS
QTL Variant Detail

Summary

• QTL variant: Lore3^LS
• Name: loss of righting induced by ethanol 3; LS
• MGI ID: MGI:2157081
• QTL: Lore3 Location: unknown Genetic Position: Chr8, Syntenic

Variant origin

• Strain of Specimen: LS

Variant description

• Allele Type: QTL
• Inheritance: Other (see notes)

Notes

Lore3 exhibits additive inheritance.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:38534

A large (LSxSS)F2 intercross was used to confirm QTLs involved in ethanol-induced sleep time and identify new QTLs. The LS (long sleep) inbred strain sleeps an average of 2 hours when administered an intraperitoneal ethanol injection. In contrast, the SS(short sleep) inbred strain sleeps an average of 10 minutes when administered an intraperitoneal ethanol injection. Lore1, previously identified in 27 LSxSS RI (recombinant inbred) strains (Bennett, J:40119), was confirmed in this study on mouse chromosome 1 spanning 43 cM - 59 cM (peak LOD = 5.4 at 54 cM). Possible candidate genes in this region are Chrnd (Acrd-acetylcholine receptor subunit delta) and Chrng (Acrg-acetylcholine receptor subunit gamma) at 52.3 cM. Lore2 on chromosome 2 spanning 78 cM - 95 cM (peak LOD = 6.6 at 85 cM) was also confirmed. A possible candidate gene for Lore2 is Ntsr at 107 cM on chromosome 2. New QTLs Lore3 (chromosome 8 spanning 44 cM - 71 cM, peak LOD = 3.4 at 59 cM), Lore4 (chromosome 11 spanning 44 cM - 56 cM, peak LOD = 6.5 at 49 cM), and Lore5 (chromosome 15 spanning 32 cM - 55 cM, peak LOD = 4.0 at 46 cM) were mapped. Suggestive QTLs Lore6 mapped to chromosome 18 (spanning 24 cM - tel, peak LOD = 1.8 at 41 cM) and Lore7 mapped to chromosome 7 (spanning 25 cM - 61 cM,peak LOD = 1.7 at 50 cM). Lore1 - Lore7 are inherited in an additive fashion. Lore1, Lore2, Lore4, and Lore5 map near QTLs associated with NT (neurotensin) receptor density. No evidence of epistasis between Lore1 - Lore7 was detected. Loci associated with blood ethanol concentration (BEC) were also analyzed in the (LSxSS)F2 population. SS mice wake with higher BEC than LS mice. 6 putative BEC QTLs (LOD = 2.0 - 3.0) were identified on chromosomes 2, 8, 9, 22, 14, and 15, and will be further analyzed for confirmation.

J:114558

Analysis of 75 LXS (L= LS long sleep inbred strain; S=SS short sleep inbred strain) recombinant inbred strains replicated and confirmed previously identified QTLs associated with ethanol-induced loss or righting reflex Lore1, Lore3, Lore4, Lore5, and Lore6. Animals were tested for loss of righting reflex (n=952) and blood ethanol concentration after i.p. injection (n=814) between 55-65 days of age. Over 4000 polymorphic SNPs were used for genotype analysis. Three different methods of QTL mapping were employed: R/qtl, QTL Cartographer, and WebQTL. No sex-specific loci were identified.

Lore1 at 54 cM on mouse Chromosome 1 was replicated, however there is evidence for a second linked locus more distal between 103 Mb - 173 Mb (LOD=2.8). This new locus isdesignated Lore9 (loss of righting induced by ethanol 9). Lore9 appears to have a stronger effect in females compared to males.

A suggestive locus on mouse Chromosome 3 from a previous study was replicated in the present study at approximately 62 cM or133 Mb - 151.7 Mb (LOD=3.28). This locus is named Lore10 (loss of righting induced by ethanol 10) and maps near D3Mit127 (70.3 cM) and D3Mit86 (76.2 cM). Lore10 appears to have a stronger effect in males compared to females.

Lore3 at 59 cM on mouse Chromosome 8 was replicated in this study and the QTL interval was narrowed to 102 Mb - 128.3 Mb using SNP analysis. Slc6a2 (formerly NET; 45 cM) is a strong candidate gene for Lore3 as exons 4 and 11 are polymorphic between parental strains LS and SS.

Haplotype analysis excluded Slc6a4 (42 cM) as a potential candidate gene for Lore4 (49 cM) on mouse Chromosome 11.

Linkage to loss of righting reflex mapped to 71 Mb - 97.7 Mb on mouse Chromosome 14 in the current study (LOD=2.77). This locus is designated Lore11 (loss of righting induced by ethanol 11). Lore11 is associated with DNA markers D14Mit228 (46 cM) and D14Mit97 (58 cM).

Lore6 on mouse Chromosome 18 was replicated in this study and the QTL interval was narrowed to 77 Mb - 89.2 Mb using SNP analysis.

References

• Original: J:38534 Markel PD, et al., Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice. Genome Res. 1997 Feb;7(2):92-9
• All: 2 reference(s)