4
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Application of Mouse Models to Research in Hearing and Balance

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="d1801674e125">Laboratory mice ( <i>Mus musculus</i>) have become the major model species for inner ear research. The major uses of mice include gene discovery, characterization, and confirmation. Every application of mice is founded on assumptions about what mice represent and how the information gained may be generalized. A host of successes support the continued use of mice to understand hearing and balance. Depending on the research question, however, some mouse models and research designs will be more appropriate than others. Here, we recount some of the history and successes of the use of mice in hearing and vestibular studies and offer guidelines to those considering how to apply mouse models. </p><div class="section"> <a class="named-anchor" id="d1801674e130"> <!-- named anchor --> </a> <h5 class="section-title" id="d1801674e131">Electronic supplementary material</h5> <p id="d1801674e133">The online version of this article (doi:10.1007/s10162-016-0589-1) contains supplementary material, which is available to authorized users. </p> </div>

          Related collections

          Most cited references 239

          • Record: found
          • Abstract: found
          • Article: not found

          High-resolution genetic mapping using the Mouse Diversity outbred population.

          The JAX Diversity Outbred population is a new mouse resource derived from partially inbred Collaborative Cross strains and maintained by randomized outcrossing. As such, it segregates the same allelic variants as the Collaborative Cross but embeds these in a distinct population architecture in which each animal has a high degree of heterozygosity and carries a unique combination of alleles. Phenotypic diversity is striking and often divergent from phenotypes seen in the founder strains of the Collaborative Cross. Allele frequencies and recombination density in early generations of Diversity Outbred mice are consistent with expectations based on simulations of the mating design. We describe analytical methods for genetic mapping using this resource and demonstrate the power and high mapping resolution achieved with this population by mapping a serum cholesterol trait to a 2-Mb region on chromosome 3 containing only 11 genes. Analysis of the estimated allele effects in conjunction with complete genome sequence data of the founder strains reduced the pool of candidate polymorphisms to seven SNPs, five of which are located in an intergenic region upstream of the Foxo1 gene.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth.

            Age-related and noise-induced hearing losses in humans are multifactorial, with contributions from, and potential interactions among, numerous variables that can shape final outcome. A recent retrospective clinical study suggests an age-noise interaction that exacerbates age-related hearing loss in previously noise-damaged ears (Gates et al., 2000). Here, we address the issue in an animal model by comparing noise-induced and age-related hearing loss (NIHL; AHL) in groups of CBA/CaJ mice exposed identically (8-16 kHz noise band at 100 dB sound pressure level for 2 h) but at different ages (4-124 weeks) and held with unexposed cohorts for different postexposure times (2-96 weeks). When evaluated 2 weeks after exposure, maximum threshold shifts in young-exposed animals (4-8 weeks) were 40-50 dB; older-exposed animals (> or =16 weeks) showed essentially no shift at the same postexposure time. However, when held for long postexposure times, animals with previous exposure demonstrated AHL and histopathology fundamentally unlike unexposed, aging animals or old-exposed animals held for 2 weeks only. Specifically, they showed substantial, ongoing deterioration of cochlear neural responses, without additional change in preneural responses, and corresponding histologic evidence of primary neural degeneration throughout the cochlea. This was true particularly for young-exposed animals; however, delayed neuropathy was observed in all noise-exposed animals held 96 weeks after exposure, even those that showed no NIHL 2 weeks after exposure. Data suggest that pathologic but sublethal changes initiated by early noise exposure render the inner ears significantly more vulnerable to aging.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A high-resolution association mapping panel for the dissection of complex traits in mice.

              Systems genetics relies on common genetic variants to elucidate biologic networks contributing to complex disease-related phenotypes. Mice are ideal model organisms for such approaches, but linkage analysis has been only modestly successful due to low mapping resolution. Association analysis in mice has the potential of much better resolution, but it is confounded by population structure and inadequate power to map traits that explain less than 10% of the variance, typical of mouse quantitative trait loci (QTL). We report a novel strategy for association mapping that combines classic inbred strains for mapping resolution and recombinant inbred strains for mapping power. Using a mixed model algorithm to correct for population structure, we validate the approach by mapping over 2500 cis-expression QTL with a resolution an order of magnitude narrower than traditional QTL analysis. We also report the fine mapping of metabolic traits such as plasma lipids. This resource, termed the Hybrid Mouse Diversity Panel, makes possible the integration of multiple data sets and should prove useful for systems-based approaches to complex traits and studies of gene-by-environment interactions.
                Bookmark

                Author and article information

                Journal
                Journal of the Association for Research in Otolaryngology
                JARO
                Springer Nature
                1525-3961
                1438-7573
                December 2016
                October 17 2016
                December 2016
                : 17
                : 6
                : 493-523
                Article
                10.1007/s10162-016-0589-1
                5112220
                27752925
                © 2016

                Comments

                Comment on this article