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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Transgenic and gene targeting studies of hair cell function in mouse inner ear.

Despite the rapid discovery of a large number of genes in sensory hair cells of the inner ear, the functional roles of these genes in hair cells remain largely undetermined. Recent advances in transgenic and gene targeting technologies in mice have offered unprecedented opportunities to genetically manipulate the expression of these genes and to study their functional roles in hair cells in vivo. Transgenic analyses have revealed the presence of hair-cell-specific promoters in the genes encoding Math1, myosin VIIa, Pou4f3, and the alpha9 subunit of the acetylcholine receptor (alpha9 AChR). Targeted inactivation using embryonic stem cell technology and transgenic expression studies have revealed the roles of several genes involved in hair cell lineage (Math1), differentiation (Pou4f3), mechanotransduction (Myo1c, and Myo7a), electromotility (Prestin), and efferent modulation (Chrna9, encoding alpha9 AChR). Although many of these genes also play roles in other tissues, inactivation of these genes in hair cells alone will soon be possible by using the Cre-loxP system. Also imminent is the development of genetic methods to inactivate genes specifically in mouse hair cells at a desired time, by using inducible systems established in other types of neurons. Combining these types of manipulation of gene expression will enable hearing researchers to elucidate some of the fundamental and unique features of hair cell function such as mechanotransduction, frequency tuning, active mechanical amplification, and efferent modulation.[1]


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