Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice.
The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177-187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN+/-mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN-/-mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN-/-mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene.
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Mo
M
Chen
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Qin
Q
Wang
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Gang-Hua
GH
Zhu
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China. Electronic address: hupeng726@126.com.
Peng
P
Hu
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Yuan
Y
Zhou
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Tian
T
Wang
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Ruo-Sha
RS
Lai
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Zi-An
ZA
Xiao
Institute of Otology, Department of Otolaryngology and Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, People's Republic of China.
Ding-Hua
DH
Xie
D000818:Animals; D003638:Deafness / Q000235:genetics* / Q000473:pathology*; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000648:ultrastructure*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology*; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D059547:Stereocilia / Q000378:metabolism / Q000473:pathology*
D011506:Proteins; C548552:taperin protein, mouse
Hearing loss; Knockout; Steriocilia; Taperin