TY - JOUR
T1 - Scleraxis is required for differentiation of the stapedius and tensor tympani tendons of the middle ear.
AU - Wang, Lingyan
AU - Bresee, Chris S.
AU - Jiang, Han
AU - He, Wenxuan
AU - Ren, Tianying
AU - Schweitzer, Ronen
AU - Brigande, John V.
N1 - Funding Information:
We thank Doris K. Wu (National Institute on Deafness and other Communication Disorders [NIDCD]) for providing the Acan and Atoh1 in situ hybridization probes; Dennis R. Trune and Beth J. Kempton for expert guidance with ABRs and GMA histochemistry; Brian A. Pryce and Spencer S. Watson for assistance with Scx mouse breeding; Jonathan Jungwirth for technical assistance with tissue dissection; and Patreece Suen for help with in situ hybridization. This work was supported by grants from the NIDCD and the National Institute of Arthritis and Musculoskeletal and Skin Diseases: DC R01 008595 and DC R01 008595-03S2 (to JB); P30 DC005983; R01 DC04554 (to TR); and R01 AR055640 (to RS).
PY - 2011/8
Y1 - 2011/8
N2 - Scleraxis (Scx) is a basic helix-loop-helix transcription factor expressed in tendon and ligament progenitor cells and the differentiated cells within these connective tissues in the axial and appendicular skeleton. Unexpectedly, we found expression of the Scx transgenic reporter mouse, Scx-GFP, in interdental cells, sensory hair cells, and cochlear supporting cells at embryonic day 18.5 (E18.5). We evaluated Scx-null mice to gain insight into the function of Scx in the inner ear. Paradoxical hearing loss was detected in Scx-nulls, with ~50% of the mutants presenting elevated auditory thresholds. However, Scx-null mice have no obvious, gross alterations in cochlear morphology or cellular patterning. Moreover, we show that the elevated auditory thresholds correlate with middle ear infection. Laser interferometric measurement of sound-induced malleal movements in the infected Scx-nulls demonstrates increased impedance of the middle ear that accounts for the hearing loss observed. The vertebrate middle ear transmits vibrations of the tympanic membrane to the cochlea. The tensor tympani and stapedius muscles insert into the malleus and stapes via distinct tendons and mediate the middle ear muscle reflex that in part protects the inner ear from noise-induced damage. Nothing, however, is known about the development and function of these tendons. Scx is expressed in tendon progenitors at E14.5 and differentiated tenocytes of the stapedius and tensor tympani tendons at E16.5-18.5. Scx-nulls have dramatically shorter stapedius and tensor tympani tendons with altered extracellular matrix consistent with abnormal differentiation in which condensed tendon progenitors are inefficiently incorporated into the elongating tendons. Scx-GFP is the first transgenic reporter that identifies middle ear tendon lineages from the time of their formation through complete tendon maturation. Scx-null is the first genetically defined mouse model for abnormal middle ear tendon differentiation. Scx mouse models will facilitate studies of tendon and muscle formation and function in the middle ear.
AB - Scleraxis (Scx) is a basic helix-loop-helix transcription factor expressed in tendon and ligament progenitor cells and the differentiated cells within these connective tissues in the axial and appendicular skeleton. Unexpectedly, we found expression of the Scx transgenic reporter mouse, Scx-GFP, in interdental cells, sensory hair cells, and cochlear supporting cells at embryonic day 18.5 (E18.5). We evaluated Scx-null mice to gain insight into the function of Scx in the inner ear. Paradoxical hearing loss was detected in Scx-nulls, with ~50% of the mutants presenting elevated auditory thresholds. However, Scx-null mice have no obvious, gross alterations in cochlear morphology or cellular patterning. Moreover, we show that the elevated auditory thresholds correlate with middle ear infection. Laser interferometric measurement of sound-induced malleal movements in the infected Scx-nulls demonstrates increased impedance of the middle ear that accounts for the hearing loss observed. The vertebrate middle ear transmits vibrations of the tympanic membrane to the cochlea. The tensor tympani and stapedius muscles insert into the malleus and stapes via distinct tendons and mediate the middle ear muscle reflex that in part protects the inner ear from noise-induced damage. Nothing, however, is known about the development and function of these tendons. Scx is expressed in tendon progenitors at E14.5 and differentiated tenocytes of the stapedius and tensor tympani tendons at E16.5-18.5. Scx-nulls have dramatically shorter stapedius and tensor tympani tendons with altered extracellular matrix consistent with abnormal differentiation in which condensed tendon progenitors are inefficiently incorporated into the elongating tendons. Scx-GFP is the first transgenic reporter that identifies middle ear tendon lineages from the time of their formation through complete tendon maturation. Scx-null is the first genetically defined mouse model for abnormal middle ear tendon differentiation. Scx mouse models will facilitate studies of tendon and muscle formation and function in the middle ear.
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U2 - 10.1007/s10162-011-0264-5
DO - 10.1007/s10162-011-0264-5
M3 - Article
C2 - 21399989
AN - SCOPUS:80054784077
SN - 1525-3961
VL - 12
SP - 407
EP - 421
JO - Journal of the Association for Research in Otolaryngology : JARO
JF - Journal of the Association for Research in Otolaryngology : JARO
IS - 4
ER -