**5. Conclusions**

In this chapter, we attempt to highlight several issues regarding the identification of background effects in mice. To identify the modifiers underlying genetic background effects, several strains were established for QTL and GWAS. Thus, the technologies for forward genetics in mice have enabled important breakthroughs and will contribute to the identification of new loci and genes associated with hearing loss. The reverse genetics approach has also been developed based on technological innovations, that is, genome editing and will be increasingly applied. An increasing number of studies have reported that the hearing loss phenotype resulting from a single gene mutation in humans is modulated by the genetic background in which the mutation is maintained (e.g., see [67].). Using genome editing, mutations discovered in the genetic background of patients with hearing loss can be conveniently manipulated in mice, and the effects of the candidate mutation can be confirmed *in vivo* by phenotypic analyses of mice.

*Csp.His55Asn*: a histidine-to-asparagine substitution at amino acid position 55 of citrate synthase

Effects of Genetic Background on Susceptibility and the Acceleration of Hearing Loss in Mice

http://dx.doi.org/10.5772/intechopen.72469

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*Fscn2p.Arg109His*: an arginine-to-histidine substitution at amino acid position 109 amino acid of

(CS) protein

CSS: consomic (chromosome substitution) strains

DPOAE: distortion product otoacoustic emission

*Gipc3*: GIPC PDZ domain containing family member 3

*Hfhl1*, *2* and *3*: loci for high-frequency hearing loss in mice

dB SPL: decibel sound pressure level

GWAS: genome-wide association study

HMDP: hybrid mouse diversity panel

*Map1a*: microtubule-associated protein 1

*moth1*: modifier of tubby hearing

*mt-TrArg*: mitochondrial tRNA-Arg NIHL: noise-induced hearing loss

QTN: quantitative trait nucleotides

SNP: single nucleotide polymorphism

*Snhl*: a locus for sensorineural hearing loss in mice

RIS: recombinant inbred strain

*Nox3*: NADPH oxidase-3

QTL: quantitative trait loci

sgRNA: single guide RNA

HDR: homology-directed repair HFHL: high-frequency hearing loss

DO: diversity outcross stock

eQTL: expression QTL *Fscn2*: fascin 2 gene

fascin 2 (FSCN2) protein

HS: heterogeneous stock

kHz: kilohertz KI: knock-in KO: knock-out

ms: milliseconds

OS: outbred stock
