Gipc3^{ahl5-Black Swiss}
QTL Variant Detail

Summary

• QTL variant: Gipc3^{ahl5-Black Swiss}
• Name: GIPC PDZ domain containing family, member 3; age related hearing loss 5-Black Swiss
• MGI ID: MGI:3622811
• Synonyms: Gipc3^343A
• QTL: Gipc3 Location: Chr10:81171099-81179100 bp, - strand Genetic Position: Chr10, 39.72 cM

Variant origin

• Strain of Specimen: Black Swiss

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: A G to A (G343A) nucleotide substitution in exon 2 of the Gipc3 gene that results in the amino acid substitution of glycine for arginine at position 115 within the PDZ domain (aa107-174). This allele confers increased hearing threshold compared to CAST/EiJ. (J:105889, J:170227)
• Inheritance: Recessive

Notes

Animals homozygous for Black Swiss-derived alleles at Ahl5 and Ahl6 exhibit significantly increased hearing threshold.

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

J:105889

QTL linked to age related hearing loss were mapped in a (Black Swiss x CAST/EiJ)F1 x Black Swiss backcross. Backcross animals were genotyped at 131 polymorphic loci. Parental strain Black Swiss exhibits early onset progressive hearing loss with moderate to severe hearing impairment by 4 weeks of age.

Significant linkage to hearing loss using the 16 kHz trait mapped to mouse Chromosome 10 near D10Mit20 (35 cM) with LOD=8.9. This locus, named Ahl5 (age related hearing loss 5), was replicated in a (Black Swiss x CAST/EiJ)F2 intercross population (LOD=7 at D10Mit139). Ahl5 also shows significant linkage to the 8 kHz trait. F2 interval mapping localized the 95% confidence interval to 27 cM - 51 cM between D10Mit38 and D10Mit95. Ahl5 explains 61% of the phenotypic variance. Animals homozygous for Black Swiss-derived alleles at Ahl5 exhibit increased hearing threshold in decibel sound pressure level (dB SPL) compared to heterozygous animals. Interaction between Ahl5 and a locus at D13Mit19 reached suggestive level of statistical significance (LOD=3.9). Cdh23 and Pcdh15 are potential candidate genes mapping to the Ahl5 95% confidence interval. However, SNP comparison of these 2 genes did not appear to indicate an association with hearing impairment. Apreviouslyidentified hearing impairment locus named jams1 (43.5 cM) maps near Ahl5.

Ahl6 (age related hearing loss 6) using the 16 kHz trait mapped to 44 cM on mouse Chromosome 18 in the (Black Swiss x CAST/EiJ)F1 x Black Swiss backcross near D18Mit103 (LOD=3.8) but was not detected in the F2 intercross. This locus explains 32% of the phenotypic variation and also shows suggestive linkage to the 8 kHz trait. Composite inteval mapping localized the Ahl6 95% confidence interval to 38 cM - 44 cM between D18Mit208 and D18Mit103. Backcross animals homozygous for Black Swiss-derived alleles at Ahl6 did not differ from that of hearing animals, however animals doubly homozygous at Ahl5 and Ahl6 exhibit significantly increased hearing threshold in dB SPL. Hearing threshold in double homozygotes increases with age. Possible interaction between Ahl6 and a locus at D13Mit19 reached LOD=2.7.

References

• Original: J:105889 Drayton M, et al., Mapping quantitative trait loci for hearing loss in Black Swiss mice. Hear Res. 2006 Feb;212(1-2):128-39
• All: 2 reference(s)