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研究生:洪惠媚
研究生(外文):Huei Mei
論文名稱:語言學習前非症候群感因神經聽障基因CONNEXIN29,CONNEXIN43和Pseudo CONNEXIN43基因突變之功能研究
論文名稱(外文):Functional study of mutant Cx29, Cx43 and pseudo-Cx43 in prelingual non-syndromic sensorineural deafness
指導教授:李宣佑李宣佑引用關係
指導教授(外文):Shuan-Yow Li
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:114
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中文摘要
聽障可因遺傳基因突變或環境因素,或兩者兼之引起。約有1/1000嬰兒在出生時或在小孩早期(即語言學習前時期prelingual period)罹患重度聽障(severe or profound),在已開發國家約有60%個案是遺傳因素所造成的。到目前為止已知有59個基因發生突變會造成遺傳性聽障,各基因的致病機制不盡相同,非常複雜。Connexin (Cx) 是個龐大的家族,它所構成的gap junction channels負責調控生理和發育過程及離子與小分子的交流。每六個Cxs 形成一個hemichannel(connexon),再由兩個hemichannels組成一個gap junction。本研究主要是利用細胞模式來探討Cx29與Cx43基因突變造成聽障的致病機制。
首先我們利用分子生物學的方法,先選殖出正常的Cx29與Cx43的基因與建構Cx29(E269D)與Cx43基因突變(S69P、T326I與932 delC)的表現載體,並進一步的將這些表現載體送入HeLa細胞中。利用細胞免疫染色法觀察到正常和異常Cx29與Cx43蛋白的表現位置。另外,我們利用microinjection的方式將Lucifer yellow染劑注入兩個鄰近有gap junction形成的HeLa細胞中的其中一個,並在注入染料3~5分鐘後,利用螢光顯微鏡觀察染料的轉移情形,來探討突變是否造成gap junction功能的影響。
本研究的結果,在Cx29基因研究方面,我們利用含螢光蛋白為質體的基因重組技術,使用微脂粒法基因轉殖感染HeLa 細胞,再利用免疫螢光染色法觀察正常或突變Cx29在細胞內的表現位置,結果發現正常Cx29-EGFP 融合蛋白表現在細胞膜,而Cx29E269D-EGFP 融合蛋白堆積在細胞質,進一步的研究發現是堆積在內質網(ER)。使用tet-on雙邊蛋白表現系統實驗的結果顯示Cx29E269D 突變會對正常Cx29造成顯性抑制效應(dominant negative effect),使正常Cx29蛋白與突變Cx29(E269D)蛋白共同堆積在細胞質。
在Cx43和ΨCx43 (psueudogene)基因研究方面,我們同樣利用HeLa細胞來研究正常或突變Cx43蛋白在細胞內表現的位置,本研究共分析Cx43基因的三個突變點:S69P(ΨCx43),932delC(ΨCx43)和T326I(Cx43)。結果發現含有 S69P、T326I和932del這三個突變的表現質體所轉殖的HeLa細胞,其突變蛋白並沒有影響蛋白運送到細胞膜,即此三種突變蛋白和正常的Cx43蛋白一樣被運送到細胞膜上形成gap junction。進一步了解Cx43三種突變基因(S69P、T326I與932delC)對gap junction功能性的影響,我們利用Lucifer yellow染劑通透實驗,發現表現S69P與T326I的兩種細胞,其染劑無法通透相鄰細胞,顯示S69P與T326I兩種突變蛋白確實會影響gap junction的功能,在另一個表現932delC的細胞中染劑對部份相鄰細胞具有通透能力,然而還是影響到gap junction的功能。
綜合以上的結果,我們已經利用分子生物學和細胞生物學的方法,建構正常及突變的Cx29和Cx43質體並表現於HeLa細胞中及進行功能性的研究,本研究使我們更深入解Cx29與Cx43突變基因造成聽障的致病機轉。


Hearing loss, caused by gene mutations and environmental factors, is a common sensory disorder in the human population. In the developed countries, the incidence of congenital hearing loss is estimated at 1 in 1000 births, of which approximately 60% cases are attributed to genetic factors. To date, 59 auditory genes have been identified.
Connexin (Cx) belongs to a large gene family, and the products of Cx gene family constitute a gap junction channel responsible for regulation of the physiological and developmental process, involving the exchange of ions and small molecules. Every six Cxs compose a hemichannel (so called as connexon), and then two hemichannel to form an integral gap junction. This study applied cell model to determine the Cx29 and Cx43 gene mutations in the pathogenic mechanisms causing hearing loss.
To confirm the localization patterns seen in the immunolabeling assay, HeLa cells were transfected with Cx29 constructs that were directly ‘tagged’ with GFP or DsRed at the C-terminal end of the protein. The results reveal the Cx29WT-EGFP was expressed along apposed cell membranes in the fluorescent localization assay with a continuous staining. In contrast, the p.E269D- EGFP (missense mutation) resulted in the accumulation of the Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the plasma membrane. Co-expression of Cx29WT and Cx29E269D proteins by a bi-directional tet-on expression system demonstrated that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the formation of the gap junction. Assuming these findings, we suggest that Cx29E269D has a dominant negative effect on the formation of the gap junction.
To determine the crucial relationship between wild type Cx43 and three of mutant Cx43 genes( S69P、T326Iand 932 del C) were cloned and their functions were analysed in HeLa cells. Localization assay of WT Cx43 reveals a typical punctuate fluorescence pattern of a gap junction channel between neighboring expression cells. Additionally, immunoblotting analysis of the transfectants confirms the production of mutant proteins, in which their distributions along appositional membranes are determined using immunofluorescent staining procedures. Furthermore, dye transfer assay results demonstrate that gap junctional intercellular communication (GJIC) is less in HeLa cells carrying mutant GJA1 orψGJA1 gene than in WT-expressing cell.
In summary, we use molecular biology methods to create the normal and mutant constructs containing Cx29 or Cx43 gene and determine the pathogenic effects of normal and mutant Cx29or Cx43 gene in transfected HeLa cells. Our data reveal the Cx29 and Cx43 gene mutations play causal roles in the pathogenesis of hearing loss.


謝誌 I
縮寫字對照表 III
中文摘要 1
英文摘要 3
序論 (Introduction) 5
材料與方法 (Materials and Methods) 17
結果 (Results) 38
討論 (Discussions) 45
圖 (Figure) 53
表 (Table) 70
附圖(Suppl. Figure) 72
附表(Suppl. Table) 83
參考文獻 (References) 86
附錄 (Appendixes) 98
Paper

1.Ahmad S, Martin PE, Evans WH (2001) Assembly of gap junction channels: mechanism, effects of calmodulin antagonists and identification of connexin oligomerization determinants. Eur J Biochem. 268:4544-52.
2.Ahmad S, Chen S, Sun J, Lin X (2003) Connexins 26 and 30 are co-assembled to form gap junctions in the cochlea of mouse. Bioche and Biophy Res Comm 307:362-368.
3.Ahn M, Lee J, Gustafsson A, Enriquez A, Lancaster E, Sul JY, Haydon PG, Paul DL, Huang Y, Abrams CK, Scherer SS (2008) Cx29 and Cx32, two connexins expressed by myelinating glia, do not interact and are functionally distinct. J Neurosci Res 86:992–1006
4.Altevogt BM, Paul DL, Goodenough DA (2000) Cloning and characterization of a novel central nervous system specific connexin, mouse connexin29. Mol Biol Cell 11:1713
5.Baille MF, Arnaud C, Cans C, Grandjean H, du Mazaubrum C, Rumeau-Rouquette C (1996) Prevalence, etiology and care of severe and profound hearing loss. Archives of Disease in childhood. 75: 129-132
6.Beltramello M, Bicego M, Piazza V, Ciubotaru CD, Mammano F, D’Andrea P (2003) Permeability and gating properties of human connexins 26 and 30 expressed in HeLa cells. Biochem Biophys Res Comm 305:1024–1033
7.Betts MJ, Russell RB (2003) Amino acid properties and consequences of subsitutions. In Bioinformatics for Geneticists p289-316. Edited by: Barnes MR, Gray IC. West Sussex, United Kingdom: Wiley and Sons.
8. Berezin C, Glaser F, Rosenberg J, Paz I, Pupko T, Fariselli P, Casadio R, Ben-Tal N (2004) ConSeq: the identification of functionally and structurally important residues in protein sequences. Bioinformatics 20:1322–1324
9.Britz-Cunningham SH, Shah MM, Zuppan CW, Fletcher WH (1995) Mutations of the connexin43 gap-junction gene in patients with heart malformations and defects of laterality. New Engl J Med 332:1323–1329
10.Bruzzone R, White TW, Paul DL (1996) Connections with connexins the molecular-basis of direct intercellular singnalling. Eur J Biochem 238:1-27
11.Corcos IA, Meess EU, Loch-Caruso R (1993) Human connexin 43 gene locus, GJA1, sublocalized to band 6q21-q23.2. Cytogenet Cell Genet 64:31–32
12.Cox JS, Shamu CE, Walter P (1993) Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell 73:1197–1206
13.Dbouk HA, Mroue RM, El-Sabban ME, Talhouk RS (2009): Connexin: a myriad of functions extending beyond assembly of gap junction channels. Cell Communication and signaling 4:1-17
14.Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, Osborn AH, Dahl HH, Middleton A, Houseman MJ, Dode C, Marlin S, Boulila-ElGaied A, Grati M, Ayadi H, BenArab S, Bitoun P, Lina-Granade G, Godet J, Mustapha M, Loiselet J, El Zir E, Aubois A, Joannard A, Petit C (1997) Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet 6:2173–2177
15.Dermietzel R, Spary DC (1993) Gap junction in the brain: where, what type, how many, and why?Trends Neurosci 16:186-192
16.Evans WH, Ahmad S, Diez J, George CH, Kendall JM, Martin PE (1999) Traffecking pathways leading to the formation of gap junctions. Novartis Found Symp 219:44–54
17.Falk MM, Kumar NM, Gilula NB (1994) Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins. J Cell Biol 127:343–355
18.Falk MM, Buehler LK, Kumar NM, Gilula NB (1997) Cell-free synthesis of connexins into functional gap junction membrane channels. EMBO J 10:2703–2716
19.Falk MM, Gilula NB (1998) Connexin membrane protein biosynthesis is influenced by polypeptide positioning within the translocon and signal peptidase access. J Biol Chem 273:7856–7864
20.Fishman GI, Moreno AP, Spray DC, Leinwand LA (1991) Functional analysis of human cardiac junction channel mutants. Proc Natl Acad Sci USA 88:3525–3529
21.Forge A, Becker D, Casalotti S, Edwards J, Evans WH, Lench N , Souter M (1999) Gap junctions and connexin expression in the inner ear. Found Symp 219: 134-150.
22.Fribley A, Zhang K, Kaufman R (2008) Regulation of Apoptosis by the unfolded protein response. Methods Mol Biol 559:191–204
23.George CH, Martin PE, Evans WH (1998) Rapid determination of gap junction formation using HeLa cells microinjected with cDNAs encoding wild-type and chimeric connexins. Biochem Biophys Res Commun 247:785–789
24.Goodenough DA, Goliger JA, and Paul DL (1996) Connexins,connexons and interceullar communction. Annu Ren Biochem 65:475-502
25.Grifa A, Wagner CA, D’Ambrosio L, Melchionda S, Bernardi F, López-Bigas N, Rabionet R, Arbones M, Monica MD, Estivill X, Zelante L, Lang F, Gasparini P (1999) Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat Genet 23:16–18
26.Guilford P, Ben Arab S, Blanchard S, Levilliers J, Weissenbach J, Belkahia A and Petit C (1994) A non-syndrome form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q. Nat Genet 6:24-28
27.Guilford P, Dode C, Crozet F, Blanchard S, Chaib H, Levilliers J, Levi-Acobas F, Weil D, Weissenbach J, Cohen D and et al (1995) A YAC contig and an EST map in the pericentromeric region of chromosome 13 surrounding the loci for neurosensory nonsyndromic deafness (DFNB1 and DFNA3) and limb-girdle muscular dystrophy type 2C (LGMD2C). Genomics 29:163-169
28.Hervé JC, Plaisance I, Loncarek J,Duthe F, Sarrouilhe D (2004) Is the junctional uncoupling elicited in rat ventricular myocytes by some dephosphorylation treatments due to changes in the phosphorylation status of Cx43? Eur Biophs J 33:201-10
29.Kalatzis V and Petit C (1998) The fundamental and medical impacts of recent progress in research on hereditary hearing loss. Hum Mol Genet 7: 1589-1597
30.Kandouz M, Bier A, Carystinos GD, Alaoui-Jamali MA, Batist G (2004) Connexin43 pseudogene is expressed in tumor cells and inhibits growth. Oncogene 23:4763–4770
31.Keats BJ and Berlin CI (1999) Genomics and hearing impairment. Genome Res 9: 7-16.
32.Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM (1997) Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387:80–83
33.Kikuchi T, Kimura RS, Paul DL and Adams JC (1995) Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat Embryol 191:101-118
34.Kleopa KA, Orthmann JL, Enriquez A, Paul DL and Scherer SS(2004) Unique Distributions of the GapJunction Proteins : Connexin29, Connexin32, and Connexin 47 in Oligodendrocytes. Glia 47:346-357.
35.Konishi T, Harick DE and Walsh PJ (1978) Ion transport in guinea pig cochlea. I. Potassium and sodium transport. Acta Otolaryngol 86: 22-34
36.Koreen IV, Elsayed W, Liu YJ, and Harris AL (2004) Tetracycline regulated expression enables purification and functional analysis of recombinant connexin channels from mammalian cells. Biochem J 383: 111-119.
37.Koval M, Harley JE, Hick E, Steinberg TH (1997) Connexin 46 is retained as monomers in a trans-Golgi compartment of osteoblastic cells. J Cell Biol 137:847–857
38.Krutovskikh V, Yamasaki H (2000) Connexin gene mutations in human genetic diseases. Muta Res 462:197–207
39.KumarN M, Gilula N B (1996) The gap junction communication channel. Cell 84:381–388.
40.Laird DW, Castillo M, Kasprzak L (1995) Gap junction turnover, intracellular traffcking, and phosphorylation of connexin43 in brefeldin treated rat mammary tumor cells. J Cell Biol 131:1193–1203

41.Laird DW (2006) Life cycle of connexins in health and disease. Biochem. J. 94: 527–543
42.Lampe PD,Lau AF(2004) The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol 36:1171-8
43.Lauf U, Giepmans BN, Lopez P, Braconnot S, Chen SC, Falk MM (2002) Dynamic traffcking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells. Proc Natl Acad Sci USA 99:10446–1045
44.Lautermann J, ten Cate WJ, AltenhoffP, Grummer R,Traub O, Jahnke K,Winterhager E(1998) Expression of the gap-junction connexins 26 and 30 in the rat cochlea. Cell Tissue Res 294: 415-420.
45.Lehninger AL, Nelson DL, Cox MM (2000) Principles of biochemistry, 3rd edn. W.H. Freeman New York. p153-156
46.Lerer I, Sagi M, Ben-Neriah Z, Wang T, Levi H, Lim DJ , Kalinec F (1998) Cell and molecular basis of hearing. Kidney Int Suppl 65: S104-113.
47.Lim DJ, Kalinec F (1998) Cell and molecular basis of hearing. Kidney Int 53:S104-S113.
48.Liu XZ, Xia XJ, Adams J, Chen ZY, Welch KO, Tekin M, Ouyang XM, Kristiansen A, Pandya A, Balkany T, Arnos KS, Nance WE (2001) Mutations in GJA1 (connexin 43) are associated with nonsyndromic autosomal recessive deafness. Hum Mol Genet 10:2945–2951
49.Li X, Lynn B.D, Olson C, Meier C, Davidson KG, Yasumura T, Rash JE, Nagy J.I (2002) Connexin 29 expression, immunocytochemistry and freeze-fracture replica immunogold labeling (FRIL) in sciatic nerve. Eur J Neurosci 16: 95-806
50.López-Bigas N, Melchionda S, Gasparini P, Borragán A, Arbonés ML, Estivill X (2002) A common frameshift mutation and other variants in GJB4 (Connexin 30.3): analysis of hearing impairment families. Hum Mut 19:458
51.Luppari R and Arslan E (1996) Neonatal screening: risk factors and outcome in 4400 children. Acta Qtorhinolaryngologia Italica 16:501-507
52.Lynch ED, Lee MK, Morrow JE, Welcsh PL, Leon PE and King MC (1997) Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science 278:1315-1318.
53.Marziano NK, Casalotti SO, Portelli AE , Becker DL, Forge A (2003) Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30. Hum Mol Genet. 12:805-812.
54.Martin PEM, Evans W.H (2000) Trafficking and targeting of connexin 32mutations to gap junctions in Charcot-Marie-Tooth X-linked disease. Curr Top Memb 49: 461-481.
55.Marazita ML, Ploughman LM, Rawling B, Remington E, Amos KS and Nance WE (1993) Genetic epidemiological studies of early-onset deafness in the U.S school-age population.Am J Med Genet. 46:486-491
56.Martin PEM, Mambetisaeva ET, Archer DA, George CH, Evans WH (2000) Analysis of gap junction assembly using mutated connexins detected in Charcot-Marie-Tooth-X-linked disease. J Neurochem 4: 711-720
57.Marziano N.K, Casalotti SO (2003) Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect onconnexin 30. Hum Mol Genet 12:805-812
58.Morton CC (2002) Genetics, genomics and gene discovery in the auditory system. Hum Mol Genet 11:1229–1240
59.Murakami S, Muramatsu T, Shimono M (2001) Expression and localization of connexin 43 in rat incisor odontoblasts. Anat Embryol (Berl) 203:367-74.
60.Musil LS, Goodenough DA (1991) Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junction plaques. J Cell Biol 115:1357–1374
61.Musil LS, Goodenough DA (1993) Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Cell 74:1065–1077
62.Nadol JB (1993) Hearing loss. New Engl J Med 329:1092–1102
63.Naeem Z and Newton V (1996) Prevalence of sensori-neural hearing loss in Asian children. Brit J Audio 30:332-339
64.Naz S, Giguere CM, Kohrman DC, Mitchem KL, Riazuddin S, Morell RJ, Ramesh A, Srisailpathy S, Deshmukh D, Riazuddin S, Griffith AJ, Friedman TB, Smith RJH and Wilcox ER (2002) Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus. Am J Hum Genet 71: 632-636
65.Pallares-Ruiz N, Blanchet P, Mondain M, Claustres M, Roux AF (2002) A large deletion including most of GJB6 in recessive nonsyndromic deafness: a digenic effect? Eur J Hum Genet 10:72–76
66.Paulson AF, Lampe PD, Meyer RA, TenBroek E, Atkinson MM, Walseth TF, Johnson RG (2000) Cyclic AMP, LDL trigger a rapid enhancement in gap junction assembly through a stimulation of connexin traffcking. J Cell Sci 113:3037–3049
67.Paznekas WA, Boyadjiev SA, Shapiro RE, Daniels O, Wollnik B, Keegan CE, Innis JW, Dinulos MB, Christian C, Hannibal MC, Jabs EW (2003) Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet 72:408–418
68.Penuela S, Bhalla R, Gong XQ, Cowan KN, Celetti SJ, Cowan BJ, Bai D, Shao Q, Laired DW (2007) Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci 120:3772–3783
69.Qu C, Gardner P, Schrijver I (2009) The role of the cytoskeleton in the formation of gap junctions by Connexin 30. Exp Cell Res 315 :1683-92.
70.Reaume AG, de Sousa PA, Kulkarni S, Langille BL, Zhu D, Davies TC, Juneja SC, Kidder GM, Rossant J (1995) Cardiac malformation in neonatal mice lacking connexin43. Science 267:1831–1834
71.Richard G , Rouan F, Willoughby CE,Brown N, Chung P, Ryynanen M,Jabs EW, Bale SJ, DiGiovanna JJ. Uitto J, Russell (2002) Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis–ichthyosis– deafness syndrome. Hum Genet 70:1341–1348.
72.Ron D (2004) Unfolded protein responses. Encycl Biol Chem 4:319–325
73.Sarma JD, Wang F, Koval M (2002) Targeted gap junction protein constructs reveal connexin-specfic differences in oligomerization. J Biol Chem 277:20911–20918
74.Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC (2003) Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev 83:1359–1400
75.Schulte BA and Steel KP (1994) Expression of α and β subunit isoforms of Na, K-AT pase in the mouse inner ear and changes with mutations at the Wv or Sid loci. Hear Res 78: 65-76
76.Sohl G, Eiberger J, Jung YT, Kozak CA, and Willecke K(2001) The mouse gap junction gene connexin29 is highly expressed in sciatic nerve and regulated during brain development. J Bio. Chem382: 973-978.
77.Sohl G, Willecke K (2004) Gap junctions and the connexin protein family. Cardiovasc Res 62: 228-32
78.Solan JL, Lampe PD (2009) Connexin 43 phosphorylation: structural changes and biological effects. Biochem J 418:261-272
79.Sonntag S, Sohl G, Dobrowolski R, Zhang MT, Winterhager E, Bukauskas FF, Willecke K (2009) Mouse lens connexin23 (Gje1) does not form functional gap junction channels but causes enhanced ATP release from HeLa cells. Eur J Cell Bio 88:65–77
80.Spicer S S; Schulte B A (1998) Evidence for a medial K+ recycling pathway from inner hair cells. The Anatomical record 251:97-113
81.Steel KP, Barkway C and Bock GR (1987) Strial dysfunction in mice with cochleo-saccular abnormalities. Hear Res 27: 11-26
82.Tang W, Zhang Y, Chang Q, Ahmad S, Dahlke I, Yi H, Chen P, Paul DL, Lin X (2006) Connexin29 is highly expressed in cochlear Schwann cells, and it is required for the normal development and function of the auditory nerve of mice. J Neurosci 26:1991–1999
83.Wada J, Kambayashi J, Marais DC and Thaimann R, (1979) Vascular perfusion of the cochlea: effect of potassium-free and rubidium-substituted media. Arch Otorhinolaryngol 225: 79-81
84.Wang YC, Kung CY, Su MC, Su CC, Hsu HM, Tsai CC, Lin CC, Li SY (2002)Mutations of Cx26 gene (GJB2) for prelingual deafness in Taiwan. Europ J Hum Genet 10: 495-49
85.Wen-Hung Wang, Jiann-Jou Yang ,Yen-Chun Lin , Jen-Tsung Yang and Shuan-Yow Li (2010) Novel expression patterns of connexin 30.3 in adult rat cochlea. Hearing Research 265:77-82
86.White T W, Bruzzone R (1996) Multiple connexin proteins in single ntercullar channels: connexin compatibility and function consequences. J Bioener Biomembr 28: 339-350.
87.Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M, Deutsch U, Sohl G (2002) Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem 383: 725–737.
88.Xia JH, Liu CY, Tang BS, Pan Q, Huang L, Dai HP, Zhang BR, Xie W, Hu DX, Zheng D, Shi XL, Wang DA, Xia K, Yu KP, Liao XD, Feng Y, Yang YF, Xiao JY, Xie DH, Huang JZ (1998) Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat Genet 20: 370-373
89.Yang JJ, Liao PJ, Su CC, Li SY (2005) Expression patterns of connexin 29 (GJE1) in mouse and rat cochlea. Biochem Biophys Res Comm 338:723–728
90.Yang JJ, Huang SH, Chou KH, Liao PJ, Su CC, Li SY (2007) Identification of mutations in members of connexin gene family as a cause of nonsyndromic deafness in Taiwan. Audiol Neurootol 12:198–208
91.Zhang K, Kaufman RJ (2004) Signaling the unfolded protein response from the endoplasmic reticulum. J Biol Chem 279:25935–25938
92.Zhang JT, Nicholson BJ (1994) The topological structure of connexin 26 and its distribution compared to connexin 32 in hepatic gap junction. J Membr Biol 139:15-29.

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