Afteq3^ISS
QTL Variant Detail

Summary

• QTL variant: Afteq3^ISS
• Name: acute functional tolerance to ethanol QTL 3; ISS
• MGI ID: MGI:5908141
• QTL: Afteq3 Location: unknown Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: ISS

Variant description

• Allele Type: QTL

Notes

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

J:237755

In the current study acute functional tolerance (AFT) to the effects of alcohol were mapped using an LXS RI panel. The LXS recombinant inbred (RI) mouse strain panel was created from pairs of ILS (inbred long sleep) / ISS (inbred short sleep) - derived F2 offspring.

An average of 12 male mice per strain (between 65 to 89 days of age) from each of the 57-59 LXS RI strains were administered a single intraperitoneal (i.p.) injection of vehicle (saline) or alcohol (ethanol; 5 g/kg, 20% v/v in saline) on day one. This was referred to as the pretreatment dose. The loss of righting reflex (LORR) was assessed in both groups using the Ponomarev and Crabbe (2002) method 24 hours following the pretreatment. The LORR test dose was 4.1 g/kg which had been found to elicit a desirable range of sleep times among the LXS; i.e., approximately 30 to 180 minutes (Bennett et al., 2006).

Immediately after alcohol injection (ip), the mouse was placed in a closed Plexiglas cylinder that was rotated 90 every 23s. Loss of righting was defined as the time at which the mouse remained supine for at least 5 seconds; at that time, the mouse was removed from the tube and a retro-orbital blood sample was drawn for determination of BEC at the loss of righting reflex (BEC1). The mouse was then tested for recovery of LORR every 3 to 6 minutes thereafter. When the animal was able to right itself within a 5 second period, it was removed from the tube and a second blood sample was drawn (BEC2). Duration of LORR (sleep time; ST) was defined as the elapsed time between collection of BEC1 and BEC2. An increase in BEC2 from BEC1 was interpreted as development of AFT and was quantified as the difference between the two.

QTL mapping was conducted at the Phenogen site (http://phenogen.ucdenver.edu/Phenogen) (Bennett et al., 2011) using a weighted marker regression on strain means (Carlborg et al., 2005). Genotypes were collected by Dr. Gary Churchill and colleagues at The Jackson Laboratory using the Affymetrix Mouse Diversity Genotyping Array (http://cgd.jax.org/mda/v1).

Table 1:

Overall, nine suggestive (genome-wide p-value <0.63; Lander and Kruglyak, 1995) and one significant (genome-wide p-value<0.05) QTL were mapped.

The significant QTL for the alcohol pretreatment group, Afteq3 ( acute functional tolerance to ethanol QTL 3) mapped to Chromosome 4 peaking at 129.798 Mb with a LOD score of 4.62 and a p value of 0.007. The ILS allele was the high allele.

The credible interval of the significant chromosome 4 QTL spanned 23 Mb and included 716 annotated genes of which 150 had at least one non-synonymous SNP or small indel that differed between the ILS and ISS; expression of 48 of the genes was cis-regulated. Enrichment analysis indicated broad functional categories underlying AFT including proteolysis, transcription regulation, chromatin modification, protein kinase activity, apoptosis, and others.

References

• Original: J:237755 Bennett B, et al., Quantitative trait locus mapping of acute functional tolerance in the LXS recombinant inbred strains. Alcohol Clin Exp Res. 2015 Apr;39(4):611-20
• All: 1 reference(s)