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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (6) : 690-704    https://doi.org/10.1007/s11684-018-0638-8
RESEARCH ARTICLE
Tprn is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice
Yuqin Men1, Xiujuan Li2, Hailong Tu1, Aizhen Zhang1, Xiaolong Fu1, Zhishuo Wang1, Yecheng Jin1, Congzhe Hou3, Tingting Zhang1, Sen Zhang1, Yichen Zhou1, Boqin Li4,5, Jianfeng Li6, Xiaoyang Sun1(), Haibo Wang6(), Jiangang Gao1()
1. School of Life Science, Shandong University, Jinan 250100, China
2. Rizhao Polytechnic, Rizhao 276826, China
3. The Second Hospital of Shandong University, Jinan 250033, China
4. Electron Microscopy Laboratory, Shandong Institute of Otolaryngology, Jinan 250022, China
5. Laboratory of Electron Microscopy, Jinan WEI-YA Biotech Company, Jinan 250100, China
6. Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
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Abstract

Tprn encodes the taperin protein, which is concentrated in the tapered region of hair cell stereocilia in the inner ear. In humans, TPRN mutations cause autosomal recessive nonsyndromic deafness (DFNB79) by an unknown mechanism. To determine the role of Tprn in hearing, we generated Tprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background. We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of Tprn-null mice starting from postnatal day 30. Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts. The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings. Radixin, a protein expressed at stereocilia tapering, was abnormally dispersed along the stereocilia shafts in Tprn-null mice. The expression levels of radixin and β-actin significantly decreased. We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet. Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet, which resulted in damage to stereociliary bundles and hearing impairments. The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79.

Keywords TPRN      stereocilia      stereociliary rootlet      actin filament      CRISPR/Cas9      hearing     
Corresponding Authors: Xiaoyang Sun,Haibo Wang,Jiangang Gao   
Just Accepted Date: 10 May 2018   Online First Date: 31 August 2018    Issue Date: 16 December 2019
 Cite this article:   
Yuqin Men,Xiujuan Li,Hailong Tu, et al. Tprn is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice[J]. Front. Med., 2019, 13(6): 690-704.
 URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0638-8
http://academic.hep.com.cn/fmd/EN/Y2019/V13/I6/690
Fig.1  CRISPR/Cas9-mediated generation of Tprn-null mice. (A) Diagram of stereociliary bundles in cochlear hair cells. The core of the stereocilia is composed of actin filaments. A tapered structure is located in the basal region of the stereocilia near the insertion site on the apical surface of the hair cell. (B) Schematic of the strategy. The target site (blue arrowhead) is located in exon 1 after the initiation codon ATG (green arrow). Red represents the protospacer adjacent motif (PAM) sequence. (C) DNA sequencing of the PCR products from WT and TPRN mutant mice at F0. The sequencing chromatograms show two mutation types. The red boxed area represents the initiation codon ATG. Red arrows signify the start sites of the mutations in mutants 1 and 2. (D) Sequences of the two mutation types (43- and 1-bp deletions). Both mutations can cause a frameshift in the TPRN gene. (E) Mouse genotyping by PCR analysis of Tprn-null mice (43-bp deletion). Lanes: heterozygous (+/-), WT (+/+), and homozygous mice (-/-). The PCR products of the WT allele was 443 bp long, the PCR products of the heterozygous TPRN null alleles were 400 and 443 bp long, and the PCR product of the homozygous TPRN null allele was 400 bp long.
Fig.2  Expression pattern of TPRN in cochlear hair cells of WT mice. (A) Gross morphology of P21 WT and Tprn-null mice. No obvious difference, including that in the body size, was noted. Scale bar: 1 cm. (B) Confocal images of cochlear hair cells stained with anti-taperin antibody in P30 WT and Tprn-null mice. TPRN was enriched at the basal tapered region of stereociliary bundles in cochlear hair cells (arrows) in the WT mice. Taperin expression was not detected in the cochlear hair cells of Tprn-null mice. The inserts represent high-magnification views of the boxed areas. Red, phalloidin; green, TPRN. Scale bar: 20 mm.
Fig.3  ABR test in WT and Tprn-null mice at different ages. (A) ABR measurements for broadband click in the 1, 2, 4, and 6 month-old mice. (B–E) ABR measurements for frequency-specific pure tone stimulation in the 1, 2, 4, and 6 month-old mice. (F) Hearing thresholds by ABR testing for frequency-specific pure tone stimulation in Tprn-null mice at 1 and 6 months of age. The data indicated a progressive elevation of thresholds from 1 month to 6 months of age. * P<0.05; ** P<0.01; *** P<0.001 compared with the WT thresholds at the corresponding frequency as determined by Student’s t-test; n>4.
Fig.4  Immunostaining of whole-mount cochleae from WT and Tprn-null mice. (A) Confocal images of hair cells stained with the F-actin dye phalloidin, the hair cell marker myosin VIIa (red), the OHC lateral membrane marker prestin (green), and the cell-nucleus-specific dye DAPI (blue) in 1 month-old mice. No obvious defect was found in the hair cells of the Tprn-null mice. Scale bars: 20 mm. (B) Confocal images of hair cells stained with phalloidin, myosin VIIa (red), prestin (green), and DAPI (blue) in 4 month-old mice. The morphology of the hair cells appears normal. Scale bars: 20 mm. (C) High-magnification images of stereociliary bundles show evident gaps in the stereociliary bundle and indicate a loss of stereocilia in the 4 month-old Tprn-null mice (arrowheads). Scale bars: 20 mm. (D) Confocal images of hair cells stained with myosin VIIa (green) in 6 month-old mice. A severe hair cell loss was observed in the basal turn of cochlea in TPRN-null mice. Scale bars: 50 mm.
Fig.5  SEM images of stereocilia in Tprn-null mice. (A) Images of hair cell bundles in the WT and Tprn-null mice at 1 month of age. (B) Images of hair cell bundles in the WT and Tprn-null mice at 2 months of age. (C) Images of hair cell bundles in the WT and Tprn-null mice at 4 months of age. Scale bars: 10 mm for HCs; 2 mm for OHCs; 5 mm for IHCs.
Fig.6  Defects in the tapered region of stereocilia and some elongated stereocilia in Tprn-null mice. (A) SEM images of stereocilia in mice at P12, P14, P30, P60, and P120. The diameters of the tapered region in the stereocilia were thinner in the Tprn-null mice than in the WT mice, starting from 1 month of age. Red inserts represent a high-magnification view of the red boxed areas. Highly magnified images of stereociliary bundles show evident gaps in the stereocilia of Tprn-null mice at P120. Scale bar: 5 mm. (A?) Statistical analysis of the diameters of the tapered region in the innermost row of stereocilia. OHCs were selected in the same region at the midbasal turn of the cochlea, and the diameters of the tapered region in the stereocilia were measured. Data are shown as the mean±standard error around the mean. Significance was calculated by Student’s t-test. *P<0.05; ** P<0.01; *** P<0.001; n>10. (B) SEM images of stereocilia at the apical turn of the cochlear OHCs at the ages of 1, 2, and 4 months.
Fig.7  Disrupted structure of stereociliary rootlets in TPRN-null mice. (A) TEM images of the vertical ultrathin sections of hair cells at the middle–basal turns of the cochlea in the 2 month-old mice. In the WT mice, the stereociliary rootlets of the stereocilia were straight (white arrowheads) and penetrating into the cuticular plate. By contrast, the stereociliary rootlets curved (black arrowheads) in the Tprn-null mice. Scale bars: 500 nm. (B) TEM images of the horizontal sections of stereociliary bundles in the 2 month-old mice. In the WT hair cells, an electron-dense central core and a peripheral-dense ring around the stereociliary rootlets were observed at the stereocilium base (white arrowheads). In the Tprn-null mice, a loose peripheral ring was observed surrounding the core actin structure (white arrowheads) but not in the WT mice. Scale bars: 500 nm. (C) High-magnification view of the red boxed areas in Fig.7B. In the WT hair cells, horizontal sections showed a uniformly aligned electron-dense central core (yellow arrowheads) (black arrows) on the apical surface of cochlear hair cells. In the Tprn-null mice, the core of stereociliary rootlets shows an evident hollow structure (yellow arrowheads). The stereociliary rootlets in the three rows were arranged disorderly (black arrows). Scale bar: 200 nm.
Fig.8  Analysis of mechanotransduction channels in the hair cells of Tprn-null mice. FM1-43 uptake assay in the hair cells of WT and Tprn-null mice at 4 months of age. The FM1-43 assay in the WT mice displayed high FM1-43 uptake, whereas the TPRN-null hair cells exhibited very low FM1-43 uptake.
Fig.9  Ectopic localization of radixin and decreased levels of radixin and b-actin in TPRN-null cochleae. (A, B) Radixin protein localization in the hair cells of 2 month-old mice. (A) In the WT mice, radixin staining was mainly detected at the base of the stereociliary bundles. (B) In the Tprn-null mice, radixin was diffusely distributed along the stereocilia shafts. (a1, a2; b1, b2) Boxed areas represent the high-magnification view in the WT mice (a1, a2) and Tprn-null mice (b1, b2). Red, phalloidin; green, radixin. Scale bars: 20 mm. (C, D) Western blot analysis of radixin (C) and b-actin (D) protein levels in the mouse cochleae at P30. (C) Radixin protein quantification indicated that the expression levels were significantly decreased in the Tprn-null mice. (D) b-actin protein quantification denoted that the expression levels were significantly decreased in the Tprn-null mice. The data were normalized against the results of the WT mice. Error bars indicate the standard error around the mean. * P<0.05; ** P<0.01; *** P<0.001 compared with the WT mice by Student’s t-test; n=3. (E) Model of actin filament core and actin-binding proteins, including taperin, at the tapered region of stereocilia. Fam65b formed a circumferential ring-like structure at the tapered region of stereocilia. TPRN was inside the ring-like structure and formed a protein complex with Clic5 and radixin. The TPRN-related protein complex could stabilize membrane/actin filament linkages in the cochlear stereocilia, including stereociliary rootlets. The dense structure of actin filaments in a stereociliary rootlet was critical for maintaining and stabilizing stereocilia.
1 MC Holley. Keynote review: The auditory system, hearing loss and potential targets for drug development. Drug Discov Today 2005; 10(19): 1269–1282
https://doi.org/10.1016/S1359-6446(05)03595-6 pmid: 16214671
2 JT Corwin, ME Warchol. Auditory hair cells: structure, function, development, and regeneration. Annu Rev Neurosci 1991; 14(1): 301–333
https://doi.org/10.1146/annurev.ne.14.030191.001505 pmid: 2031573
3 LG Tilney, JC Saunders. Actin filaments, stereocilia, and hair cells of the bird cochlea. I. Length, number, width, and distribution of stereocilia of each hair cell are related to the position of the hair cell on the cochlea. J Cell Biol 1983; 96(3): 807–821
https://doi.org/10.1083/jcb.96.3.807 pmid: 6682110
4 DN Furness, S Mahendrasingam, M Ohashi, R Fettiplace, CM Hackney. The dimensions and composition of stereociliary rootlets in mammalian cochlear hair cells: comparison between high- and low-frequency cells and evidence for a connection to the lateral membrane. J Neurosci 2008; 28(25): 6342–6353
https://doi.org/10.1523/JNEUROSCI.1154-08.2008 pmid: 18562604
5 U Müller, PG Barr-Gillespie. New treatment options for hearing loss. Nat Rev Drug Discov 2015; 14(5): 346–365
https://doi.org/10.1038/nrd4533 pmid: 25792261
6 R Fettiplace, KX Kim. The physiology of mechanoelectrical transduction channels in hearing. Physiol Rev 2014; 94(3): 951–986
https://doi.org/10.1152/physrev.00038.2013 pmid: 24987009
7 LH Gagnon, CM Longo-Guess, M Berryman, JB Shin, KW Saylor, H Yu, PG Gillespie, KR Johnson. The chloride intracellular channel protein CLIC5 is expressed at high levels in hair cell stereocilia and is essential for normal inner ear function. J Neurosci 2006; 26(40): 10188–10198
https://doi.org/10.1523/JNEUROSCI.2166-06.2006 pmid: 17021174
8 R Goodyear, G Richardson. Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear. J Comp Neurol 1992; 325(2): 243–256
https://doi.org/10.1002/cne.903250208 pmid: 1281174
9 DW Anderson, FJ Probst, IA Belyantseva, RA Fridell, L Beyer, DM Martin, D Wu, B Kachar, TB Friedman, Y Raphael, SA Camper. The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Hum Mol Genet 2000; 9(12): 1729–1738
https://doi.org/10.1093/hmg/9.12.1729 pmid: 10915760
10 T Hasson, PG Gillespie, JA Garcia, RB MacDonald, Y Zhao, AG Yee, MS Mooseker, DP Corey. Unconventional myosins in inner-ear sensory epithelia. J Cell Biol 1997; 137(6): 1287–1307
https://doi.org/10.1083/jcb.137.6.1287 pmid: 9182663
11 F Pataky, R Pironkova, AJ Hudspeth. Radixin is a constituent of stereocilia in hair cells. Proc Natl Acad Sci USA 2004; 101(8): 2601–2606
https://doi.org/10.1073/pnas.0308620100 pmid: 14983055
12 S Bau, N Schracke, M Kränzle, H Wu, PF Stähler, JD Hoheisel, M Beier, D Summerer. Targeted next-generation sequencing by specific capture of multiple genomic loci using low-volume microfluidic DNA arrays. Anal Bioanal Chem 2009; 393(1): 171–175
https://doi.org/10.1007/s00216-008-2460-7 pmid: 18958448
13 Y Li, E Pohl, R Boulouiz, M Schraders, G Nürnberg, M Charif, RJ Admiraal, S von Ameln, I Baessmann, M Kandil, JA Veltman, P Nürnberg, C Kubisch, A Barakat, H Kremer, B Wollnik. Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss. Am J Hum Genet 2010; 86(3): 479–484
https://doi.org/10.1016/j.ajhg.2010.02.003 pmid: 20170898
14 AU Rehman, RJ Morell, IA Belyantseva, SY Khan, ET Boger, M Shahzad, ZM Ahmed, S Riazuddin, SN Khan, S Riazuddin, TB Friedman. Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79. Am J Hum Genet 2010; 86(3): 378–388
https://doi.org/10.1016/j.ajhg.2010.01.030 pmid: 20170899
15 FT Salles, LR Andrade, S Tanda, M Grati, KL Plona, LH Gagnon, KR Johnson, B Kachar, MA Berryman. CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI. Cytoskeleton (Hoboken) 2014; 71(1): 61–78
https://doi.org/10.1002/cm.21159 pmid: 24285636
16 B Zhao, Z Wu, U Müller. Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. eLife 2016; 5: 5
https://doi.org/10.7554/eLife.14222 pmid: 27269051
17 M Chen, Q Wang, GH Zhu, P Hu, Y Zhou, T Wang, RS Lai, ZA Xiao, DH Xie. Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice. Biochem Biophys Res Commun 2016; 479(4): 703–707
https://doi.org/10.1016/j.bbrc.2016.09.148 pmid: 27693694
18 QY Zheng, KR Johnson, LC Erway. Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear Res 1999; 130(1-2): 94–107
https://doi.org/10.1016/S0378-5955(99)00003-9 pmid: 10320101
19 Y Fujihara, M Ikawa. CRISPR/Cas9-based genome editing in mice by single plasmid injection. Methods Enzymol 2014; 546: 319–336
https://doi.org/10.1016/B978-0-12-801185-0.00015-5 pmid: 25398347
20 KA Steigelman, A Lelli, X Wu, J Gao, S Lin, K Piontek, C Wodarczyk, A Boletta, H Kim, F Qian, G Germino, GS Géléoc, JR Holt, J Zuo. Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells. J Neurosci 2011; 31(34): 12241–12250
https://doi.org/10.1523/JNEUROSCI.6531-10.2011 pmid: 21865467
21 Y Men, A Zhang, H Li, T Zhang, Y Jin, H Li, J Zhang, J Gao. LKB1 is required for the development and maintenance of stereocilia in inner ear hair cells in mice. PLoS One 2015; 10(8): e0135841
https://doi.org/10.1371/journal.pone.0135841 pmid: 26274331
22 A Lelli, Y Asai, A Forge, JR Holt, GS Géléoc. Tonotopic gradient in the developmental acquisition of sensory transduction in outer hair cells of the mouse cochlea. J Neurophysiol 2009; 101(6): 2961–2973
https://doi.org/10.1152/jn.00136.2009 pmid: 19339464
23 RJ Goodyear, W Marcotti, CJ, Kros GP Richardson. Development and properties of stereociliary link types in hair cells of the mouse cochlea. J Comp Neurol 2005; 485(1): 75–85 doi:10.1002/cne.20513 PMID:15776440
24 S Kitajiri, K Fukumoto, M Hata, H Sasaki, T Katsuno, T Nakagawa, J Ito, S Tsukita, S Tsukita. Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia. J Cell Biol 2004; 166(4): 559–570
https://doi.org/10.1083/jcb.200402007 pmid: 15314067
25 CA Kolb, MA Käser, J Kopecký, G Zotz, M Riederer, EE Pfündel. Effects of natural intensities of visible and ultraviolet radiation on epidermal ultraviolet screening and photosynthesis in grape leaves. Plant Physiol 2001; 127(3): 863–875
https://doi.org/10.1104/pp.010373 pmid: 11706169
26 D Kopecky, M Hayde, AR Prusa, KP Adlassnig. Knowledge-based interpretation of toxoplasmosis serology test results including fuzzy temporal concepts—the ToxoNet system. Stud Health Technol Inform 2001; 84(Pt 1): 484–488
pmid: 11604787
27 SP Francis, JF Krey, ES Krystofiak, R Cui, S Nanda, W Xu, B Kachar, PG Barr-Gillespie, JB Shin. A short splice form of Xin-actin binding repeat containing 2 (XIRP2) lacking the Xin repeats is required for maintenance of stereocilia morphology and hearing function. J Neurosci 2015; 35(5): 1999–2014
https://doi.org/10.1523/JNEUROSCI.3449-14.2015 pmid: 25653358
28 BJ Perrin, DM Strandjord, P Narayanan, DM Henderson, KR Johnson, JM Ervasti. b-Actin and fascin-2 cooperate to maintain stereocilia length. J Neurosci 2013; 33(19): 8114–8121
https://doi.org/10.1523/JNEUROSCI.0238-13.2013 pmid: 23658152
29 SY Khan, S Riazuddin, M Shahzad, N Ahmed, AU Zafar, AU Rehman, RJ Morell, AJ Griffith, ZM Ahmed, S Riazuddin, TB Friedman. DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3. Eur J Hum Genet 2010; 18(1): 125–129
https://doi.org/10.1038/ejhg.2009.121 pmid: 19603065
30 L Zheng, G Sekerková, K Vranich, LG Tilney, E Mugnaini, JR Bartles. The deaf jerker mouse has a mutation in the gene encoding the espin actin-bundling proteins of hair cell stereocilia and lacks espins. Cell 2000; 102(3): 377–385
https://doi.org/10.1016/S0092-8674(00)00042-8 pmid: 10975527
31 AW Peng, IA Belyantseva, PD Hsu, TB Friedman, S Heller. Twinfilin 2 regulates actin filament lengths in cochlear stereocilia. J Neurosci 2009; 29(48): 15083–15088
https://doi.org/10.1523/JNEUROSCI.2782-09.2009 pmid: 19955359
32 G Sekerková, CP Richter, JR Bartles. Roles of the espin actin-bundling proteins in the morphogenesis and stabilization of hair cell stereocilia revealed in CBA/CaJ congenic jerker mice. PLoS Genet 2011; 7(3): e1002032
https://doi.org/10.1371/journal.pgen.1002032 pmid: 21455486
33 DN Furness, SL Johnson, U Manor, L Rüttiger, A Tocchetti, N Offenhauser, J Olt, RJ Goodyear, S Vijayakumar, Y Dai, CM Hackney, C Franz, PP Di Fiore, S Masetto, SM Jones, M Knipper, MC Holley, GP Richardson, B Kachar, W Marcotti. Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2. Proc Natl Acad Sci USA 2013; 110(34): 13898–13903
https://doi.org/10.1073/pnas.1304644110 pmid: 23918390
34 GI Frolenkov, IA Belyantseva, TB Friedman, AJ Griffith. Genetic insights into the morphogenesis of inner ear hair cells. Nat Rev Genet 2004; 5(7): 489–498
https://doi.org/10.1038/nrg1377 pmid: 15211351
35 C Petit, GP Richardson. Linking genes underlying deafness to hair-bundle development and function. Nat Neurosci 2009; 12(6): 703–710
https://doi.org/10.1038/nn.2330 pmid: 19471269
36 MC Drummond, IA Belyantseva, KH Friderici, TB Friedman. Actin in hair cells and hearing loss. Hear Res 2012; 288(1-2): 89–99
https://doi.org/10.1016/j.heares.2011.12.003 pmid: 22200607
37 H Shahin, T Walsh, T Sobe, J Abu Sa’ed, A Abu Rayan, ED Lynch, MK Lee, KB Avraham, MC King, M Kanaan. Mutations in a novel isoform of TRIOBP that encodes a filamentous-actin binding protein are responsible for DFNB28 recessive nonsyndromic hearing loss. Am J Hum Genet 2006; 78(1): 144–152
https://doi.org/10.1086/499495 pmid: 16385458
38 LG Tilney, LA Jaffe. Actin, microvilli, and the fertilization cone of sea urchin eggs. J Cell Biol 1980; 87(3): 771–782
https://doi.org/10.1083/jcb.87.3.771 pmid: 6893988
39 S Kitajiri, T Sakamoto, IA Belyantseva, RJ Goodyear, R Stepanyan, I Fujiwara, JE Bird, S Riazuddin, S Riazuddin, ZM Ahmed, JE Hinshaw, J Sellers, JR Bartles, JA Hammer 3rd, GP Richardson, AJ Griffith, GI Frolenkov, TB Friedman. Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing. Cell 2010; 141(5): 786–798
https://doi.org/10.1016/j.cell.2010.03.049 pmid: 20510926
40 J Boutet de Monvel, C Petit. Wrapping up stereocilia rootlets. Cell 2010; 141(5): 748–750
https://doi.org/10.1016/j.cell.2010.05.022 pmid: 20510920
41 TD Pollard, GG Borisy. Cellular motility driven by assembly and disassembly of actin filaments. Cell 2003; 112(4): 453–465
https://doi.org/10.1016/S0092-8674(03)00120-X pmid: 12600310
42 QY Zheng, YC Tong, KN Alagramam, H Yu. Tympanometry assessment of 61 inbred strains of mice. Hear Res 2007; 231(1-2): 23–31
https://doi.org/10.1016/j.heares.2007.05.011 pmid: 17611057
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