TY - JOUR
T1 - Glial-specific deletion of Med12 results in rapid hearing loss via degradation of the stria vascularis
AU - Huang, Teng Wei
AU - Iyer, Amrita A.
AU - Manalo, Jeanne M.
AU - Woo, Junsung
AU - Bosquez Huerta, Navish A.
AU - McGovern, Melissa M.
AU - Schrewe, Heinrich
AU - Pereira, Fredrick A.
AU - Groves, Andrew K.
AU - Ohlemiller, Kevin K.
AU - Deneen, Benjamin
N1 - Funding Information:
Received Jan. 12, 2021; revised June 11, 2021; accepted July 5, 2021. Author contributions: T.-W.H., J.W., K.K.O., and B.D. designed research; T.-W.H., A.A.I., J.M.M., J.W., N.A.B.H., and K.K.O. performed research; A.A.I., J.M.M., M.M.M., H.S., and A.K.G. contributed unpublished reagents/analytic tools; T.-W.H., A.A.I., N.A.B.H., F.A.P., and A.K.G. analyzed data; T.-W.H. and B.D. wrote the paper. This work was supported by grants from the National Multiple Sclerosis Society (FG-1607-25417, to T.-W.H.) and the National Institutes of Health (NS-071153 and NS-096096, to B.D.; and DC-014832 to A.K.G.). A.A.I. was supported in part by The Cullen Foundation. The authors declare no competing financial interests. Correspondence should be addressed to Benjamin Deneen at deneen@bcm.edu. https://doi.org/10.1523/JNEUROSCI.0070-21.2021 Copyright © 2021 the authors
Publisher Copyright:
Copyright © 2021 the authors
PY - 2021/8/25
Y1 - 2021/8/25
N2 - Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration of the stria vascularis, in conjunction with disorganization of basal cells adjacent to the spiral ligament and downregulation of key cell adhesion proteins. Physiologic analysis revealed early changes in endocochlear potential, consistent with strial-specific defects. Together, our studies reveal that Med12 regulates auditory function in the adult by preserving the structural integrity of the stria vascularis.
AB - Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration of the stria vascularis, in conjunction with disorganization of basal cells adjacent to the spiral ligament and downregulation of key cell adhesion proteins. Physiologic analysis revealed early changes in endocochlear potential, consistent with strial-specific defects. Together, our studies reveal that Med12 regulates auditory function in the adult by preserving the structural integrity of the stria vascularis.
KW - Astrocyte
KW - Hearing loss
KW - Mediator complex
KW - Stria vascularis
UR - http://www.scopus.com/inward/record.url?scp=85113877106&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0070-21.2021
DO - 10.1523/JNEUROSCI.0070-21.2021
M3 - Article
C2 - 34253626
AN - SCOPUS:85113877106
SN - 0270-6474
VL - 41
SP - 7171
EP - 7181
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 34
ER -