Cochlear Structure and Function in a Recessive Type of Genetically Induced Inner Ear Degeneration

Sjöström, Björn; Anniko, Matti

doi:10.1159/000276302

Cited by 19 publications

(25 citation statements)

References 17 publications

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“…Inner ear dysfunction in spinner mice results from mutations in Tmie, which encodes a novel protein with predicted transmembrane domains . Jerker mice, deficient in the actin bundling protein espin, exhibit a variety of hair cell defects, including shortened stereocilia by P12 [Sjostrom and Anniko, 1992a, b]. Hair cells of shaker 2 mice, which lack normal Myo15 function, also possess extremely short stereocilia bundles Probst et al, 1998].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Two Transgene Insertional Mutations at Pirouette, a Mouse Deafness Locus

Odeh¹,

Hagiwara

Skynner

et al. 2004

Audiol Neurotol

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The mouse mutant ‘pirouette’ (pi) exhibits profound hearing loss and vestibular defects due to inheritance of a recessive mutation on chromosome 5. Dysfunction has been correlated with defects during maturation of sensory cells in the inner ear. As an initial step in characterizing pirouette at the genetic level, we have localized the candidate interval to a small region on central chromosome 5 by analysis of a congenic strain of pirouette mice. This region exhibits conserved synteny with human chromosome 4 and suggests that pirouette may be a genetic model of the human nonsyndromic deafness disorder DFNB25, which has been localized to 4p15.3–q12. In addition to the original spontaneous pirouette strain, we have identified and characterized 2 additional mouse strains with allelic mutations at the same locus. Analysis of the morphology in each of the 3 pirouette alleles indicated very similar early postnatal alterations in maturation of stereocilia and suggests that the gene affected in pirouette normally plays a role in building or maintaining these structures that are critical for sensory mechanotransduction.

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Section: Discussionmentioning

confidence: 99%

Characterization of Two Transgene Insertional Mutations at Pirouette, a Mouse Deafness Locus

Odeh¹,

Hagiwara

Skynner

et al. 2004

Audiol Neurotol

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“…Assessments of hearing physiology showed that jerker mice were totally deaf from the first time point such measurements could be carried out [30,31]. Electron microscopic studies in the early 1990's revealed a pronounced shortening and degeneration of stereocilia in the cochlear hair cells of jerker mice, defects that became pronounced near the onset of hearing around postnatal day 10 [32,33]. Occasional defects, such as protrusion and folding of the cuticular plate, were also noted in the cochlear hair cells of newborn jerker mice.…”

Section: Jerker Deafness Mutation In the Mouse Espin Genementioning

confidence: 99%

“…Phenotypically, mice that are hetereozygous for the jerker mutation (jerker heterozygotes) appear relatively normal. Although aged jerker heterozygotes have been reported to show stereociliary and hair cell degeneration [32,33], it is presently unclear whether these defects are related to the jerker mutation or are associated with age-related hearing loss, which is evident in a number of inbred mouse strains [36]. Unfortunately, the reports of cochlear defects in aged jerker heterozygotes [32,33] used mice of a different background strain (CBA) as wild-type controls, and to our knowledge wild-type mice of the standard inbred jerker mouse strain (JE/LeJ, stock number 000249) obtained from the Jackson Laboratory (Bar Harbor, Maine, USA) have not yet been tested for age-related hearing loss.…”

Section: Jerker Deafness Mutation In the Mouse Espin Genementioning

confidence: 99%

“…It is possible that the stereociliary shrinkage observed in jerker mice in early postnatal life can also be traced to an ~10% difference in rates of actin polymerization and depolymerization in their PAB. The fact that stereociliary bundles form in jerker mice [32][33][34] suggests a greater requirement for espins in the postnatal elongation and steady-state length maintenance than in stereocilium formation per se. The correlation between espin protein level and stereociliary length also extends to hair cells in normal animals.…”

Section: Increasing the Steady-state Length Of Pabsmentioning

confidence: 99%

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Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

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The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca 2+ . In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. KeywordsEspin; actin; hair cell; stereocilia; microvilli; sensory; deafness; taste The stereocilia and microvilli of vertebrate sensory cells and their actinbundling proteinsMany classes of vertebrate sensory cells detect chemical or mechanical stimuli through microvilli or their derivatives, such as stereocilia. These relatively long-lived, fingerlike specializations of the plasma membrane are built around a common cytoskeletal element -the parallel actin bundle (PAB) [1]. PABs consist of tightly packed collections of actin filaments cross-linked by actin-bundling proteins. The filaments are aligned along their longitudinal axis and display a uniform polarity with respect to their preferred ends for actin monomer addition, which in microvilli and stereocilia is positioned at the distal tip. The PAB displays hallmarks of a supramolecular scaffold that determines the placement, dimensions, flexibility and signaling properties of microvilli and stereocilia. Although filopodia also contain a PAB at their core and are believed to sense the local environment, they are considerably more dynamic and differ significantly from microvilli and stereocilia in their molecular composition and biogenesis [2].

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“…There is no topographical gradient in the progression of cochlear duct pathology, which means that all parts of the cochlea become affected simultaneously. The specific degenerative changes are followed by less specific changes including shrinkage, vacuolization and ultimately total disintegration of the hair cells [7], Vestib ular hair cells are similarly affected [8], Only a few effer ent nerve endings were seen at the base of the cochlear hair cells.…”

Section: Introductionmentioning

confidence: 99%

Cochlear Synaptic Development and Morphology in a Genetically Induced Type of Progressive Hair Cell Degeneration

Sjöström

1994

ORL

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In mice with genetically induced inner ear abnormalities it is conceivable that in the morphogenetic types and in mutants with the spotting kind of pigmentary anomaly, the genes act through the developing nervous system. It has been suggested that in degenerative (neuroepithelial) mutants the influence of the gene is also reflected in the inner ear through the agency of the nervous system. The jerker mouse belongs to the neuroepithelial type of mutants which in homozygotes results in early postnatal degeneration of the sensory epithelium of the inner ear, initially confined to the cuticular plate and the stereocilia. In spite of well-advanced hair cell degeneration, these mutants developed morphologically normal afferent and efferent nerve terminals at cochlear hair cells.

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Cochlear Structure and Function in a Recessive Type of Genetically Induced Inner Ear Degeneration

Cited by 19 publications

References 17 publications

Characterization of Two Transgene Insertional Mutations at Pirouette, a Mouse Deafness Locus

Characterization of Two Transgene Insertional Mutations at Pirouette, a Mouse Deafness Locus

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Cochlear Synaptic Development and Morphology in a Genetically Induced Type of Progressive Hair Cell Degeneration

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