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On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse.

Abstract

OBJECTIVES

Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications.

METHODS

Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice.

RESULTS

We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes).

CONCLUSION

These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    1 Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 2 Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA, USA.

    ,

    1 Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

    ,

    1 Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

    1 Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 3 Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

    Source

    The Annals of otology, rhinology, and laryngology 128:6_suppl 2019 Jun pg 125S-133S

    MeSH

    Animals
    Calcium-Binding Proteins
    Disease Models, Animal
    Hair Cells, Vestibular
    Membrane Proteins
    Mice
    Mice, Knockout
    Phenotype

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31092028

    Citation

    Prins, Terry J., et al. "On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse." The Annals of Otology, Rhinology, and Laryngology, vol. 128, no. 6_suppl, 2019, 125S-133S.
    Prins TJ, Saldate JJ, Berke GS, et al. On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse. Ann Otol Rhinol Laryngol. 2019;128(6_suppl):125S-133S.
    Prins, T. J., Saldate, J. J., Berke, G. S., & Hoffman, L. F. (2019). On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse. The Annals of Otology, Rhinology, and Laryngology, 128(6_suppl), 125S-133S. doi:10.1177/0003489419834596.
    Prins TJ, et al. On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse. Ann Otol Rhinol Laryngol. 2019;128(6_suppl):125S-133S. PubMed PMID: 31092028.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse. AU - Prins,Terry J, AU - Saldate,Johnny J, AU - Berke,Gerald S, AU - Hoffman,Larry F, PY - 2019/5/17/entrez PY - 2019/5/17/pubmed PY - 2019/5/29/medline KW - bootstrap resampling KW - labyrinth KW - oncomodulin KW - sensory epithelia KW - utricle SP - 125S EP - 133S JF - The Annals of otology, rhinology, and laryngology JO - Ann. Otol. Rhinol. Laryngol. VL - 128 IS - 6_suppl N2 - OBJECTIVES: Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications. METHODS: Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice. RESULTS: We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes). CONCLUSION: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia. SN - 1943-572X UR - https://www.unboundmedicine.com/medline/citation/31092028/On_the_Legacy_of_Genetically_Altered_Mouse_Models_to_Explore_Vestibular_Function:_Distribution_of_Vestibular_Hair_Cell_Phenotypes_in_the_Otoferlin-Null_Mouse L2 - http://journals.sagepub.com/doi/full/10.1177/0003489419834596?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -