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

Acquired hearing loss, which includes age-related hearing loss and noise-induced hearing loss, is a common hearing impairment and shows phenotypic variability. One reason for phenotypic variability is influence of genetic background. The modifiers underlying genetic background are modulated and advance the hearing phenotypes through gene-gene interactions with other etiological genetic factors. Moreover, the modifiers play a role in the susceptibility of environmental hearing risk factors, namely, the strength and weakness of environmental susceptibility often modulate and advance hearing phenotypes via gene-environment interactions. The complicated gene-gene and gene-environment interactions make genetic analysis of acquired hearing loss difficult. In particular, the effects of environmental factors cannot be completely excluded or controlled. Although genome-wide approaches to identify genetic modifiers have proven challenging in humans, the responsible genes and mutations are widely unknown. In this chapter, we suggest that mouse models are useful for studying genetic background effects for acquired hearing loss. The genetic analysis of mouse models identified the genetic modifiers. We review the genetic research in mouse models for acquired hearing loss to identify and confirm the modifiers by both forward and reverse genetics approaches

Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSM/Ms Mice

An MSM/Ms strain was established using Japanese wild mice, which exhibit resistance to several phenotypes associated with aging, such as obesity, inflammation, and tumorigenesis, compared to common inbred mouse strains. MSM/Ms strain is resistant to age-related hearing loss, and their auditory abilities are sustained for long durations. The age-related hearing loss 3 (ahl3) locus contributes to age-related hearing in MSM/Ms strain. We generated ahl3 congenic strains by transferring a genomic region on chromosome 17 from MSM/Ms mice into C57BL/6J mice. Although C57BL/6J mice develop age-related hearing loss because of the ahl allele of the cadherin 23 gene, the development of middle- to high-frequency hearing loss was significantly delayed in an ahl3 congenic strain. Moreover, the novel age-related hearing loss 10 (ahl10) locus associated with age-related hearing resistance in MSM/Ms strain was mapped to chromosome 12. Although the resistance effects in ahl10 congenic strain were slightly weaker than those in ahl3 congenic strain, slow progression of age-related hearing loss was confirmed in ahl10 congenic strain despite harboring the ahl allele of cadherin 23. These results suggest that causative genes and polymorphisms of the ahl3 and ahl10 loci are important targets for the prevention and treatment of age-related hearing loss

Chromosome homology between mouse and three Muridae species, Millardia meltada, Acomys dimidiatus and Micromys minutus, and conserved chromosome segments in murid karyotypes

Comparative chromosome painting with mouse (Mus musculus, MMU) chromosome-specific DNA probes was performed for three Muridae species, the Indian soft-furred field rat (Millardia meltada), the spiny mouse (Acomys dimidiatus) and the harvest mouse (Micromys minutus). All probes except for the Y probe were successfully hybridized to the chromosomes of all species, and homologous chromosome segments between mouse and the three species were identified at the molecular level. Comparison of our data with the published data of six other genera (Mus, Rattus, Apodemus, Otomys, Rhabdomys and Cricetulus) of the Muridae suggested that the associations MMU1b/17a, 2b/13a, 5b/11a, 7/19, 10b/17b, 10c/17c, 11b/16a, 12/17d and 13b/15, and the single painted chromosomes and chromosome segments MMU3, 4, 5a, 8a, 8b, 16b, 18 and X were probably contained by the ancestral karyotype of the Muridae, and have been strongly conserved throughout murid evolution

Role of nucleocapsid protein of hantaviruses in intracellular traffic of viral glycoproteins

To understand the role of nucleocapsid protein (NP) of hantaviruses in viral assembly, the effect of NP on intracellular traffic of viral glycoproteins Gn and Gc was investigated. Double staining of viral and host proteins in Hantaan virus (HTNV)-infected Vero E6 cells showed that Gn and Gc were localized to cis-Golgi, in which virus particles are thought to be formed. When HTNV Gn and Gc were expressed by a plasmid encoding glycoprotein precursor (GPC), which is posttranslationaly cleaved into Gn and Gc, Gn was localized to cis-Golgi, whereas Gc showed diffuse distribution in the cytoplasm in 32.9% of Gc-positive cells. The ratio of the diffused Gc-positive cells was significantly decreased to 15.0% by co-expression of HTNV NP. Co-expression of HTNV GPC with NPs of other hantaviruses, such as Seoul virus, Puumala virus and Sin Nombre virus, also reduced the ratios of diffused Gc-positive cells to 13.5%, 25.2%, and 11.6%, respectively. Among amino- and carboxyl-terminally truncated HTNV NPs, NP75-429, NP116-429, NP1-333, NP1-233, and NP1-155 possessed activity to reduce the ratio of diffused Gc-positive cells, while NP155-429 and NP1-116 did not. NP30-429 has partial activity. These results indicate that amino acid region 116-155 of NP is important for the activity, although amino acid region 1-30 is partially related. Truncation of the HTNV Gc cytoplasmic tail caused an increase in diffused Gc-positive cells. In addition, the effect of coexpression of HTNV NP was weakened. These results suggest that HTNV NP has a role to promote Golgi localization of Gc through a mechanism possibly mediated by the Gc cytoplasmic tail

Species and genetic diversity of Bandicota (Murinae, Rodentia) from Myanmar based on mitochondrial and nuclear gene sequences

Bandicoot rats (genus Bandicota), widely known as rodent pests, are abundant and widespread throughout the continental part of the Indo-Malayan realm. However, their evolutionary history is not yet well understood. The molecular phylogenetic relationships of the three bandicoot rat species, Bandicota bengalensis, Bandicota indica, and Bandicota savilei, were assessed based on the gene sequences of the specimens collected from Myanmar, where all three species occur along with database sequences. Early divergence of B. savilei (1.5-1.7 million years ago) was inferred from the mitochondrial cytochrome b (Cytb) gene and the nuclear interphotoreceptor retinoid-binding protein (Irbp), and melanocortin 1 receptor (Mc1r) gene sequences. The Cytb lineage of B. bengalensis from Sri Lanka was distinct from the monophyletic lineage of the continental lineages of B. bengalensis and B. indica. This can be explained by the preservation of ancient mitochondrial DNA (mtDNA) in the insular population owing to female philopatry and male dispersal, given that no substantial intraspecies geographic subdivision was observed in the nuclear markers. The paraphyletic relationship of B. bengalensis with B. indicamay be explained by introgression of the mtDNA from B. bengalensis to B. indica, but further investigation is required to confirm this. B. bengalensis Cytb sequences from a wide area of Myanmar had limited nucleotide diversity (π = 0.00079), implying that the genetic diversity of B. bengalensisin Myanmar was acquired through Holocene human activities

Characterization of Full Genome of Rat Hepatitis E Virus Strain from Vietnam

We amplified the complete genome of the rat hepatitis E virus (HEV) Vietnam strain (V-105) and analyzed the nucleotide and amino acid sequences. The entire genome of V-105 shared only 76.8%–76.9% nucleotide sequence identities with rat HEV strains from Germany, which suggests that V-105 is a new genotype of rat HEV