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

Prins TJ1,2, Saldate JJ1, Berke GS1, Hoffman LF1,3.

Author information

1

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

2

2 Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA, USA.

3

3 Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

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.

KEYWORDS:

bootstrap resampling; labyrinth; oncomodulin; sensory epithelia; utricle

PMID:

 

31092028

 

DOI:

 

10.1177/0003489419834596

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