Mouse models of human hearing disorders

 

 

Non-syndromic     Syndromic                                                       

 

Human Non-syndromic Deafness Genes and corresponding Mouse Genes and Mutations

Human gene Human disorder Human Reference Human Chr Mouse Chr Mouse gene Mouse mutation Mouse Reference

ACTG1

DFNA20, DFNA26

Zhu et al. (2003) Am J Hum Genet 73:1082

17q25

11 (79) 

Actg1 

targeted null

 Belyantseva et al. (2009) Proc Natl Acad Sci 106:9703
BSND

DFNB7  (also Bartter syndrome, type 4A)

 Riazuddin et al. (2009) Am J Hum Genet 85:273 1p31 4 (52) Bsnd conditional null Rickheit et al. (2008) Embo J 27:2907
CCDC50 DFNA44 Modamio-Hoybjor et al. (2007) Am J Hum Genet 80:1076 3q28-q29 16 (20) Ccdc50 none

CDH23

DFNB1  (also USH1D)

Bork et al. (2001) Am J Hum Genet 68:26 1021-q22 10 (30) Cdh23 waltzer, v Palma et al. (2001) Nat Genet 27:103
CLDN14 DFNB29 Wilcox et al. (2001) Cell 104:165 21q22 16 (67) Cldn14 targeted null  Ben-Yosef et al. (2003) Hum Mol Genet 12:2049
COCH DFNA9 Robertson et al. (1998) Nat Genet 20:299 14q12-q13 12 (23) Coch targeted null, not deaf; targeted missense, late onset hearing loss

 Makishima et al. (2005) Hum Genet 118:29; Robertson et al. (2008) Hum Mol Genet 17:3426

COL11A2

DFNA13 DFNB53 (also STL2)

 McGuirt et al. (1999) Nat Genet 23:413; Chen et al. (2005) J Med Genet 42:e61 6p21 17 (19) Col11a2 targeted null McGuirt et al. (1999) Nat Genet 23:413

CRYM

DFNA (undefined locus number)

Abe et al. (2003) Am J Hum Genet 72:73

16p13-p12

7  (55)

Crym

 targeted null, but normal hearing Suzuki et al. (2007) Mol Endocrinol 21:885
DFNA5 DFNA5 Van Laer et al. (1998) Nat Genet 20:194 7p15 6 (23) Dfna5h targeted null, but not deaf  Van Laer et al. (2005) Neurobiol Dis 19:386

DFNB59  (PEJVAKIN)

 DFNB59 Delmaghani et al. (2006) Nat Genet 38:770 2q31 2 (45) Dfnb59

targeted knock-in

ENU sirtaki null

Delmaghani et al. (2006) Nat Genet 38:770; Schwander et al. (2007) J Neurosci 27:2163

DIAPH1 DFNA1 Lynch et al. (1997) Science 278:1315 5q31 18 (16) Diap1 targeted null but hearing not assessed  Peng et al. (2007) Cancer Res 67:7565; Sakata et al. (2007) J Exp Med 204:2031

ESPN

DFNB36

Naz et al. (2004) J Med Genet 41:591

1p36

4 (80)

Espn

jerker, je

Zheng et al. (2000) Cell 102:377

ESRRB DFNB35 Collin et al. (2008) Am J Hum Genet 82:125 14q24 12 (41) Esrrb targeted, conditional null  Chen and Nathans (2007) Dev Cell 13:325
EYA4 DFNA10

Wayne et al. (2001) Hum Mol Genet 10:195

 6q23 10 (18) Eya4 targeted null, model for otitis media  Depreux et al. (2008) J Clin Invest 118:651
GJB2 (CX26) DFNA3, DFNB1 Kelsell et al. (1997) Nature 387:80 13q11-q12 14 (21) Gjb2

conditional KO

dominant-negative transgene

Cohen-Salmon et al. (2002) Curr Biol 12:1106

Kudo et al. (2003) Hum Mol Genet 12:995  

GJB3 (CX31) DFNA2 (also recessive) Xia et al. (1998) Nat Genet 20:370 1p33-p35 4 (57) Gjb3 targeted null, but not good model Plum et al. (2001) Dev Biol 231:334
GJB6 (CX30) DFNA3, DFNB1 Grifa et al. (1999) Nat Genet 23:16; Del Castillo et al. (2002) N Engl J Med 346:243 13q12 14 (21) Gjb6 targeted null Teubner et al. (2003) Hum Mol Genet 12:13
GRHL2  (TFCP2L3) DFNA28 (also age-related hearing impairment) Peters et al. (2002) Hum Mol Genet 11:2877; Van Laer et al. (2008) Hum Mol Genet 17:159 8q22 15 (18) Grhl2 none
HGf DFNB39 Schultz et al. (2009) Am J Hum Genet 85:25 7q21 5 (4) Hgf conditional KO, transgene overexpression Schultz et al. (2009) Am J Hum Genet 85:25
KCNQ4 DFNA2 Kubisch et al. (1999) Cell 96:437 1p34 4 (57) Kcnq4 targeted null and knock-in Kharkovets et al. (2006) EMBO J 25:642
LOXHD1 DFNB77 Grillett et al. (2009) Am J Hum Genet 85:328 18q21 18 (50) Loxhd1 samba, ENU-induced mutation Grillett et al. (2009) Am J Hum Genet 85:328
LRTOMT DFNB63 Ahmed et al. (2008) Nat Genet 40:1335 11q13 7 (50) Lrrc51, Tomt ENU-induced mutation of Tomt Du et al. (2008) Proc Natl Acad Sci 105:14609

MARVELD2  (TRIC)

 DFNB49 Riazuddin et al. (2006) Am J Hum Genet 79:1040 5q13 13 (51) Marveld2 none
MIR96 DFNA50 Mencia et al. (2009) Nat Genet 41:609 7q32 6 (7) Mirn96 diminuendo, Dmdo (ENU) Lewis et al. (2009) Nat Genet 41:614
MYH9 DFNA17 Lalwani et al. (2000) Am J Hum Genet 67:1121 22q11 15 (43) Myh9 gene-trap null, but no hearing loss Parker et al. (2006) Brain Res 1091:235  

MYH14

DFNA4

Donaudy et al. (2004) Am M Hum Genet 74:770

19q13

7 (23) 

Myh14

none

 

MYO1A

DFNA48

Donaudy et al. (2003) Am J Hum Genet 72:1571

12q13-q14

10 (70)

Myo1a

targeted null, but not deaf

Tyska et al. (2005) Mol Biol Cell 16:2443

MYO15A DFNB3 Wang et al. (1998) Science 280:1447 17p11 11 (34) Myo15 shaker 2, sh2 Probst et al. (1998) Science 280:1444
MYO3A DFNB30 Walsh et al. (2002) Proc Natl Acad Sci USA 99:7518 10p11 2 (10) Myo3a none  
MYO6

DFNA22, DFNB37

 Melchionda et al. (2001) Am J Hum Genet 69:635; Ahmed et al. (2003) Am J Hum Genet 72:1315 6q13 9 (44) Myo6 snell's waltzer, sv Avraham et al. (1995) Nat Genet 11:379
MYO7A

DFNB2, DFNA11 (also USH1B)

 Liu et al. (1997) Nat Genet 16:188; Liu et al. (1997) Nat Genet 17:268 11q13 7 (48) Myo7a shaker 1, sh1 Gibson et al. (1995) Nature 374:62
OTOA DFNB22 Zwaenepoel et al.(2002) Proc Natl Acad Sci U S A. 99:6240 16p12 7 (57) Otoa none  
OTOF DFNB9 Yasunaga et al. (1999) Nat Genet 21:373 2p23 5 (18) Otof targeted null Roux et al. (2006) Cell 127:277 

PCDH15

DFNB23 (also USH1F)

Ahmed et al. (2003) Hum Mol Genet 12:3215

10q21-q22

10 (40.2)

Pcdh15

Ames waltzer, av

Alagramam et al. (2001) Nat Genet 27:99

POU3F4 DFN3 de Kok et al. (1995) Science 267:685 Xq21.1 X (48) Pou3f4 (Brn4)

targeted null 

 

sex-linked fidget, slf

Minowa et al. (1999) Science 285:1408; Phippard et al. (1999) J Neurosci 19:598

Phippard et al. (2000) Hum Mol Genet 9:79

POU4F3 DFNA15 Vahava et al. (1998) Science 279:1950 5q31 18 (24) Pou4f3 (Brn3c) targeted null; dreidel, ddl Erkman et al. (1996) Nature 381, 603-6; Xiang et al. (1997) Proc Natl Acad Sci USA 94:9445
RDX DFNB24 Khan et al. (2007) Hum Mutat 28:417 11q23 9 (29) Rdx targeted null Kitajiri et al. (2004) J Cell Biol 166:559
SLC17A8 DFNA25 Ruel et al. (2008) Am J Hum Genet 83:278 12q23 10 (49) Slc17a8 targeted null Seal et al. (2008) Neuron 57:263
SLC26A4

DFNB4 (also PDS)

Li et al. (1998) Nat Genet 18:215 7q31 12 (~15) Slc26a4 targeted null Everett et al. (2001) Hum Mol Genet 10:153

SLC26A5  (PRES)

DFNB61

Liu et al. (2003) Hum Mol Genet 12:1155

7q22

5 (8)

Slc26a5(Pres)

targeted null

Liberman et al. (2002) Nature 419:300

STRC DFNB16 Verpy et al. (2001) Nat Genet 29:345 15q15 2 (68) Strc targeted null  Verpy et al. (2008) Nature 456:255
TECTA DFNA8, DFNA12, DFNB21 Verhoeven et al. (1998) Nat Genet 19:60; Mustapha et al. (1999) Hum Mol Genet 8:409 11q22-q24 9 (25) Tecta

targeted null

targeted missense 

Legan et al. (2000) Neuron 28:273

Legan et al. (2005) Nat Neurosci 8:1035

TMC1

DFNB7, DFNB11, DFNA36

 Kurima et al. (2002) Nat Genet 30:277 9q13-q21 19 (15) Tmc1

deafness, dn

Beethoven, Bth

Kurima et al.(2002) Nat Genet 30:277

Vreugde et al. (2002) Nat Genet 30:257

TMHS

DFNB67

Shabbir et al. (2006) J Med Genet 43:634; Kalay et al. (2006) Hum Mutat 27:633

6p21-p22

17 (13)

Tmhs

hurry-scurry, hscy

Longo-Guess et al. (2005) Proc Natl Acad Sci USA 102:7894

TMIE DFNB6 Naz et al. (2002) Am J Hum Genet 71:632 3p21-p22 9 (61) Tmie spinner, sr Mitchem et al. (2002) Hum Mol Genet 11:1887
TMPRSS3 DFNB10, DFNB8 Scott et al. (2001) Nat Genet 27:59 21q22 17 (17) Tmprss3 none  
TRIOBP DFNB28

Riazuddin et al. (2006) Am J Hum Genet 78:137; Shahin et al. (2006) Am J Hum Genet 78:144

 22q13 15 (47) Triobp none
USH1C

DFNB18 (also USH1C)

 Ahmed et al. (2002) Hum Genet 110:527 11p15 7 (23.5) Ush1c deaf circler, dfcr Johnson et al. (2003) Hum Mol Genet 12:3075 

WFS1

DFNA6, DFNA14, DFNA38 (also WFS1)

Bespalova et al. (2001) Hum Mol Genet 10:2501; Young et al.(2001) Hum Mol Genet 10:2509

4p16

5 (21)

Wfs1

targeted null, but hearing not assessed

 Ishihara et al. (2004) Hum Mol Genet 13:1159
WHRN

DFNB31 (also USH2D)

 Mburu et al. (2003) Nat Genet 34:421 9q32-q34 4 (31) Whrn whirler, wi Mburu et al. (2003) Nat Genet 34:421

Human syndromic deafness genes and corresponding mouse genes and mutations

Human gene Human disorder Human Reference Human Chr Mouse Chr Mouse gene Mouse mutation Mouse Reference
BSND

Bartter syndrome, type 4A (also DFNB73)

 Birkenhager et al. (2001) Nat Genet 29:310 1p31 4 (52) Bsnd conditional null Rickheit et al. (2008) EMBO J 27:2907
CDH23

USH1D, Usher syndrome type ID (also DFNB12)

 Bolz et al. (2001) Nat Genet 27:108; Bork et al. (2001) Am J Hum Genet 68:26 10q21-q22 10 (30) Cdh23 waltzer, v Palma et al. (2001) Nat Genet 27:103

CHD7

CHARGE syndrome

Vissers et al. (2004) Nat Genet 36:955 

8q12

4 (2)

Chd7

Wheels, Whl, and multiple additional mutants

Bosman et al. (2005) Hum Mol Genet 14:3463

CISD2 WFS2, Wolfram syndrome 2 Amr et al. (2007) Am J Hum Genet 81:673 4q24 3 (68) Cisd2 targeted null Chen et al. (2009) Genes Dev 23:1183

CLRN1

USH3A

 USH3A, Usher syndrome type 3A Joensuu et al. (2001) Am J Hum Genet 69:1160; Adato et al. (2002) Eur J Hum Genet 10:339 3q21-q25 3 (30) Clrn1 targeted null Geng et al. (2009) Hum Mol Genet 18:2748
COL11A1 STL3, Stickler syndrome type III Richards et al. (1996) Hum Mol Genet 5:1339 1p21 3 (53) Col11a1 chondro-
dysplasia, cho		 Cho et al. (1991) Ann N Y Acad Sci 630:259; Li et al. (1995) Cell 80:423

COL11A2

 STL2, Stickler syndrome type II (also DFNA13)  Vikkula et al. (1995) Cell 80:431 6p21 17 (19) Col11a2 targeted null McGuirt et al. (1999) Nat Genet 23:413
COL1A1 OI, osteogenesis imperfecta Barsh et al. (1982) Proc Natl Acad Sci USA 79:31108; Shapiro et al. (1982) Jama 247:2120 17q21-q22 11 (56) Col1a1 Mov13
transgene disruption 		Bonadio et al. (1990) Proc Natl Acad Sci USA 87:7145; Altschuler et al. (1991) Ann N Y Acad Sci 630:249
COL2A1 STL1, Stickler syndrome type I Williams et al. (1996) Am J Med Genet 63:461 12q13 15 (55) Col2a1 dispropor-
tionate micromelia,
Dmm; spondyloepiphyseal dysplasia congenita, sedc;  mutant transgenes 		Berggren et al. (1997) Hear Res 107:125; Donahue et al. (2003) J Bone Min Res 18:1612; Maddox et al. (1998) J Craniofac Genet Dev Biol 18:195
COL4A3 Alport syndrome Mochizuki et al. (1994) Nat Genet 8:77 2q37-q37 1 (51) Col4a3 targeted null Cosgrove et al. (1998) Hear Res 121:84
COL9A1 Stickler syndrome Van Camp et al. (2006) Am J Hum Genet 79:449 6q13 1 (15) Col9a1 targeted null Suzuki et al. (2005) Neurosci Res 51:293
EDN3 WS4, Waardenburg-Shah syndrome Edery et al. (1996) Nat Genet 12:442 20q13 2 (104) Edn3 lethal spotting, ls Baynash et al. (1994) Cell 79:1277
EDNRB WS4, Waardenburg-Shah syndrome Attie et al. (1995) Hum Mol Genet 4:2407 13q22 14 (51) Ednrb piebald, s Hosoda et al. (1994) Cell 79:1267
EYA1 BOR, branchio-
oto-renal syndrome		 Abdelhak et al. (1997) Nat Genet 15:157 8q13 1 (10) Eya1 spontaneous -- Eya1 bor and targeted null Johnson et al. (1999) Human Molecular Genetics 8:645; Xu et al. (1999) Nat Genet 23:113
FGFR3 craniosyno-
stosis 		Hollway et al. (1998) Lancet 351:877 4p16 5 (20) Fgfr3 targeted null Colvin et al. (1996) Nat Genet 12:390
GATA3 HDR syndrome: hypopara
thyroidism, sensorineural deafness, and renal dysplasia		 Van Esch et al. (2000) Nature 406:419 10p15 2 (7.0) Gata3 targeted null Karis et al. (2001) J Comp Neurol 429:615

GPR98  (MASS1, VLGR1)

USH2C, Usher syndrome type 2C

Weston et al.(2004) Am J Hum Genet 74:357

5q14 

 13 (40)

Gpr98

BUB/BnJ and Frings inbred strains

targeted null    

Johnson et al. (2005) Genomics 85:582

McGee et al. (2006) J Neurosci 26:6543

KCNE1   (ISK) JLNS2, Jervell and Lange-Nielsen syndrome, locus 2 Schulze-Bahr et al. (1997) Nat Genet 17:267; Tyson et al. (1997) Hum Mol Genet 6:2179 21q22 16 (64) Kcne1 targeted null Vetter et al. (1996) Neuron 17:1251; Letts et al. (2000) Mamm Genome 11:1101
KCNQ1   (KVLQT1) JLNS1, Jervell and Lange-Nielsen syndrome, locus 1 Neyroud et al. (1997) Nat Genet 15:186 11p15 7 (43) Kcnq1 targeted null Lee et al. (2000) J Clin Invest 106:1447; Casimiro et al. (2001) Proc Nat Acad Sci USA 98:2526
KIT PBT, piebald trait Giebel and Spritz (1991) Proc Natl Acad Sci USA 88:8436 4q12 5 (42) Kit dominant spotting,W Geissler et al. (1988) Cell 55:185; Steel and Barkway (1989) Development 107:453
MITF WS2A, Waardenburg syndrome type IIA Tassabehji et al. (1994) Nat Genet 8:251 3p14-p12 6 (40) Mitf microph-
thalmia, mi 		Hodgkinson et al. (1993) Cell 74:395
MYO7A

USH1B, Usher syndrome type IB (also DFNB2, DFNA11)

Weil et al. (1995) Nature 374:60 11q13 7 (48) Myo7a shaker 1, sh1 Gibson et al. (1995) Nature 374:62
NDP ND, Norrie disease Berger et al. (1992) Nat Genet 1:199; Chen et al. (1992) Nat Genet 1:204 Xp11 X (5) Ndph targeted null Berger et al. (1996) Hum Mol Genet 5:51; Rehm et al.(2002) J Neurosci 22:4286
NOG stapes ankylosis Brown et al. (2002) Am J Hum Genet 71:618 17q22 11 (51) Nog targeted null heterozygote Hwang and Wu (2008) Hum Mol Genet 17:844
PAX2 renal-coloboma syndrome Eccles and Schimmenti (1999) Clin Genet 56:1 10q24-q25 19 (43) Pax2 targeted null Torres et al. (1996) Development 122:3381
PAX3 WS1, Waardenburg syndrome type I; WS3, Klein-Waardenburg syndrome Tassabehji et al. (1992) Nature 355:635; Hoth et al. (1993) Am J Hum Genet 52:455 2q37 1 (44) Pax3 splotch, Sp Epstein et al. (1991) Cell 67:767; Steel and Smith (1992) Nat Genet 2:75
PCDH15 USH1F, Usher syndrome type 1F (also DFNB23) Ahmed et al. (2001) Am J Hum Genet 69:25; Alagramam et al. (2001) Hum Molec Genet 10:1709 10q21-q22 10 (40.2) Pcdh15 Ames waltzer,
av		 Alagramam et al. (2001) Nat Genet 27:99
PMP22 CMT1A, Charcot-Marie-Tooth disease, type 1A Kovach et al. (1999) Am J Hum Genet 64:1580 17p11-p12 11 (34) Pmp22 trembler, Tr Suter et al. (1992) Nature 356:241; Zhou et al. (1995) Hear Res 88:87

SALL1

TBS, Townes-Brocks syndrome

Kohlhase et al. (1998) Nature Genet 18:81

16q12

8 (41)

Sall1

targeted mutation producing truncated protein

Kiefer et al. (2003) Hum Mol Genet 12: 2221

SIX1 BOS3, bronchiootic syndrome 3 Ruf et al. (2004) Proc Nat Acad Sci 101:8090 14q23 12 (31) Six1

targeted null

ENU catweasel hypomorphic 

 Zheng et al. (2003) Development 130:3989; Bosman et al. (2009) Dev Biol 328:285
SIX5 BOR2, bronchiootorenal syndrome 2 Hoskins et al. (2007) Am J Hum Genet 80:800 19q13 7 (4) Six5 targeted null Klesert et al. (2000) Nature Genet 25:105; Sarkar et al. (2000) Nature Genet 25: 110
SLC19A2 TRMA, thiamin-responsive megaloblastic anemia styndrome Labay et al., Fleming et al.,  Diaz et al., (1999) Nat Genet 22:300, 305, 309 1q23  1 (87) Slc19a2 targeted null Oishi et al. (2002) Hum Mol Genet 11:2951
SLC26A4 PDS, Pendred syndrome (also DFNB4) Everett et al. (1997) Nat Genet 17:411 7q31 12 (~15) Slc26a4 targeted null

Everett et al. (2001) Hum Mol Genet 10:153

SNAI2 

WS2, Waardenburg  syndrome, type II 

Sanchez-Martin et al. (2002) Hum Mol Genet 11:3231

8q11

16 (9)

Snai2

targeted null

 Sanchez-Martin et al. (2002) Hum Mol Genet 11:3231

SOX10 WS4, Waardenburg-Shah syndrome Pingault et al. (1998) Nat Genet 18:171 22q13 15 (47) Sox10 dominant megacolon,
Dom 		Herbarth et al. (1998) Proc Natl Acad Sci USA 95:5161; Southard-Smith et al. (1998) Nat Genet 18:60
SPTBN4 CMT4F, Charcot-Marie-Tooth disease, type 4F  not confirmed 19q13 7 (7.5) Spnb4 quivering, qv Parkinson et al.(2001) Nat Genet 29:61

TBX1

DGS, DiGeorge syndrome

Chieffo et al. (1997) Genomics 43:267

22q11

16(11) 

Tbx1 

transgene overexpression

targeted null

Funke et al. (2001) Hum Molec Genet 10:2549

Vitelli et al. (2003) Hum Molec Genet 12:2041

THRB

thyroid hormone resistance

Sakurai et al. (1989) Proc Natl Acad Sci U S A 86:8977

3p24

14 (1.5)

Thrb 

targeted null

Forrest et al. (1996) Nat Genet 13:35

USH1C USH1C, Usher syndrome type 1C (also DFNB18) Ahmed et al. (2002) Hum Genet 110:527 11p15 7 (23.5) Ush1c deaf circler, dfcr Johnson et al. (2003) Hum Mol Genet 12:3075 

USH1G  (SANS)

USH1G, Usher syndrome, type 1G

Weil et al. (2003) Hum Mol Genet 12:463

17q24-25

 11 (77)

Ush1g

Jackson shaker, js

Kikkawa et al. (2003) Hum Molec Genet 12:453

USH2A USH2A, Usher syndrome type 2A Eudy et al. (1998) Science 280:1753 1q41 1 (106) Ush2a targeted null Liu et al. (2007) Proc Natl Acad Sci USA 104:4413

WFS1

Wolfram syndrome 1 (also DFNA6, DFNA14, DFNA38)

Strom et al. (1998) Hum Molec Genet 7:2021

4p16

5 (21)

Wfs1

targeted null, but hearing not assessed

Ishihara et al. (2004) Hum Mol Genet 13:1159

WHRN USH2D, Usher syndrome type 2D (also DFNB31) Ebermann et al. (2007) Hum Genet 121:203 9q32-q34 4 (31) Whrn whirler, wi Mbura et al. (2003) Nat Genet 34:421