The Rockefeller University - Laboratory of Sensory Neuroscience

Hair Cells of the Inner Ear

Screening for Zebrafish Mutations Affecting
Hearing and Balance

Mutation of the Zebrafish's choroideremia Gene
Causes Hair-Cell Degeneration

Paravalbumin 3, A Potent Ca²⁺ Buffer in Hair Cells

Spontaneous Oscillation by Hair Bundles

Electrical Stimulation of Hair-Bundle Movement

Electron-Microscopic Tomographic Analysis of
the Transduction Element

Radixin in the hair bundle

Dynamical instability and the ear's active process

Friday, July 25, 2008




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Mutation of the Zebrafish's choroideremia Gene
Causes Hair-Cell Degeneration

Larvae from one mutant line (ru848) identified in the behavioral screen are unresponsive to vibratory stimuli but display a startle response to tactile stimulation. The animals are unable to maintain an upright orientation owing to a vestibular problem. The inner ears of mutants lack the extracellular microphonic potentials recorded in wild-type fish. When the inner ear or lateral-line organ of a five-day-old larva is exposed to a cationic fluorophore that is accumulated by wild-type hair cells, few cells are visible. The hair cells that remain in five-day-old larvae appear morphologically abnormal and show signs of membrane blebbing. In the semicircular canals, the surviving kinocilia are significantly shorter than those of wild-type hair cells. Using positional cloning techniques, we have localized the ru848 mutation to the chm gene, the zebrafish homolog of the human choroideremiagene (CHM). Mutations in the CHM gene induce choroideremia, a slowly progressive degeneration of rod photoreceptors and retinal pigment epithelial cells. This gene encodes Rab escort protein 1, a protein necessary for the prenylation and membrane association of Rabs, the small, Ras-related GTP-binding proteins involved in vesicular transport. The degenerative phenotype resulting from the ru848 mutation in the chm gene indicates that hair cells and particular retinal cells are uniquely sensitive to the loss of Rab escort protein 1 and depend on the presence of functional Rab molecules for survival.