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- Title
An Atohl-S193A Phospho-Mutant Allele Causes Hearing Deficits and Motor Impairment.
- Authors
Wei Rose Xie; Hsin-I Jen; Seymour, Michelle L.; Szu-Ying Yeh; Pereira, Fred A.; Groves, Andrew K.; Klisch, Tiemo J.; Zoghbi, Huda Y.
- Abstract
Atonal homolog 1 (Atoh1) is a basic helix-loop-helix (bHLH) transcription factor that is essential for the genesis, survival, and maturation of a variety of neuronal and non-neuronal cell populations, including those involved in proprioception, interoception, balance, respiration, and hearing. Such diverse functions require fine regulation at the transcriptional and protein levels. Here, we show that serine 193 (S193) is phosphorylated in Atohl'sbHLH domain in vivo. Knock-in mice of both sexes bearing a GFP-taggedphospho-deadS193A allele on a null background (AtohlS193A/latZ) exhibit mild cerebellar foliation defects, motor impairments, partial pontine nucleus migration defects, cochlear hair cell degeneration, and profound hearingloss. We also found that Atoh 1 heterozygous mice of both sexes (Atoh1lacZ/+) have adult-onset deafness. These data indicate that different cell types have different degrees of vulnerability to loss of Atohl function and that hypomorphic Atoh1 alleles should be considered in human hearing loss.
- Subjects
ALLELES; DEAFNESS; MOVEMENT disorders; SERINE; PHOSPHORYLATION; LABORATORY mice
- Publication
Journal of Neuroscience, 2017, Vol 37, Issue 36, p8583
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0295-17.2017