Macdq1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Macdq1^C57BL/6J
• Name: marginal cell density QTL 1; C57BL/6J
• MGI ID: MGI:6108251
• QTL: Macdq1 Location: unknown Genetic Position: Chr12, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

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

J:244553

The current study marked an exploration of the natural gene variants that modulate endocochlear potential (EP). The endocochlear potential (EP) differs between C57BL/6J (B6) and BALB/cJ (BALB) mice, being lower in BALBs by about 10 mV.

To identify genes and alleles that promote natural EP variation as well as noise related EP reduction in BALB mice, quantitative trait loci were mapped using 12 recombinant inbred (RI) strains generated from B6 and BALB mice. Physiologic recording, morphometry and mapping were conducted using C57BL/6J (B6, n=25), BALB/cJ (BALB, n=34, reciprocal F1 hybrids (n=29) and the CxB RI series of mice.

The endocochlear potential (EP) is a large positive extracellular potential (+80-110 mV, depending on species) making up part of the electrochemical gradient that drives cochlear hair cell receptor potentials. Both single unit thresholds and compound action potential (CAP) thresholds depend on the EP. Both CAP and EP recordings were conducted for each animal. Mice were 2-5 months of age at the time of evaluation.

QTL mapping was done using WebQTL at GeneNetwork (www.GeneNetwork.org) using NCBI Build 37 coordinates. Genome wide significance levels were determined by permutation testing (1000 permutations). Significant linkage was indicated at a p value of 0.05. No correlation was found between CAP thresholds and baseline EP across strains.

For unexposed mice, the strain distribution patterns for EP and marginal cell density were used to generate preliminary QTL. Suggestive regions were mapped to Chromosomes 10, 12, 13 and 15 with BALB alleles increasing EP on Chrs 13 and 15.

Mapping of mean marginal cell density by strain yielded a significant QTL, Macdq1 (marginal cell density QTL 1), on Chromosome 12 near 58 Mb, LOD=4.5. The Macdq1 interval showed general overlap with a weak QTL for EP that mapped approximately between 48-58 Mb on the same Chromosome. The B6 alleles at both intervals increased marginal cell density and EP. Candidate genes for QTL Macdq1 included Foxg1, Foxa1, Akap6, Nkx2-1 and Pax9.

QTL mapping of the EP in noise-exposed RI mice reveal four suggestive regions, two regions mapped to Chromosome 5, and one to Chr 9 and another to Chr 18.

References

• Original: J:244553 Ohlemiller KK, et al., QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice. J Assoc Res Otolaryngol. 2016 Jun;17(3):173-94
• All: 1 reference(s)