TABLE 2.
Examples of mouse models generated for studying human deafness
| Human gene | Human disorder | Mouse gene | Mouse models | Major Phenotype | Reference |
|---|---|---|---|---|---|
| PCDH15 | DFNB23 | Pcdh15 | Ames-waltzer | Deafness, circling behavior, head tossing, and hyperactivity |
Alagramam et al., 1999 |
| CDH23 | DFNB12 | Cdh23 | waltzer; waltzer niigata; mdfw;Ahl Albany-waltzer |
NSSNHL with circling behavior, head tossing, and erratic movements |
Di Palma et al., 2001; Wada et al., 2001; Bryda et al., 2001 |
| VLGR1 | USH2C (Usher syndrome Type 2C) |
Vlgr1 | BUB/BnJ and Frings inbred strains; Targeted kO |
Sound-induced seizures and progressive hearing loss |
Skradski et al., 2001; Zheng et al., 1999; Johnson et al., 2005 |
| USH2A | USH2A (Usher syndrome Type 2A) |
Ush2a | Targeted KO | Progressive blindness, moderate and nonprogressive hearing loss at higher frequencies |
Liu et al., 2007; Adato et al., 2005 |
| USH1G/SANs | USH1G (Usher syndrome, Type 1G) |
Ush1g/Sans | Jackson shaker, js | Deafness, hyperactivity, head tossing, and circling behavior |
Weil et al., 2003; Kikkawa et al., 2003 |
| USH1C | USH1C (Usher syndrome Type 1C); DFNB18 |
Ush1c | Deaf circler, dfcr | Deafness, hyperactivity, head tossing, and circling behavior |
Johnson et al., 2003; Verpy et al., 2000 |
| GJB2 | DFNA3A, DFNB1A | Gjb2 | Conditional KO; Cx26R75W | Deafness |
Cohen-Salmon et al., 2002; Wang et al., 2009; Kudo et al., 2003 |
| GJB6 | DFNA3B, DFNB1B | Gjb6 | Targeted KO | Deafness |
Sun et al., 2009; Teubner et al., 2003 |
| CLDN14 | DFNB29 | Cldn14 | Targeted KO | Deafness | Ben-Yosef et al., 2003 |
| KCNE1 | JLNS2 (Jervell and Lange-Nielsen syndrome, locus 2) |
Kcne1 | Targeted KO | Severe hearing loss and vestibular symptoms |
Vetter et al., 1996 |
| KCNQ1 | JLNS1 (Jervell and Lange-Nielsen syndrome, locus 1) |
Kcnq1 | Targeted KO | Severe hearing loss and vestibular symptoms |
Lee et al., 2000; Casimiro et al., 2001 |
| KCNQ4 | DFNA2A | Kcnq4 | Targeted KO; Dominant- negative transgene |
Progressive hearing loss within weeks. No vestibular phenotype |
Kharkovets et al., 2006 |
| SLC26A4 | DFNB4; Pendrin syndrome |
Slc26a4 | Targeted KO | Waltzer-like vestibular dysfunction and complete deafness |
Everett et al., 2001 |
| COL4A3 | Alport syndrome | Col4a3 | Targeted KO | Hearing loss was detected after 6 weeks of age. Homozygotes died at about 14 weeks due to renal failure |
Cosgrove et al., 1998 |
| COL2A1 | STL1 (Stickler syndrome Type I) |
Col2a1 | Disproportionate micromelia, Dmm; Spondyloepiphyseal dysplasia congenita, sedc; |
Dwarf, cleft palate, deafness. Died at birth due to lung hypoplasia |
Brown, 1981; Berggren et al., 1997; Donahue et al., 2003 |
| COL11A1 | STL3 (Stickler syndrome Type III) |
Col11a1 | chondrodysplasia, Cho | Cleft palate, severely hearing impaired, died soon after birth due to lethal chondrodysplasia |
Cho et al., 1991 |
| COL11A2 | STL2 (Stickler syndrome Type II); DFNA13, DFNB53 |
Col11a2 | Targeted KO | Shorter long bones, receding snouts, and hearing loss |
McGuirt et al., 1999 |
| COL9A1 | Stickler syndrome | Col9a1 | Targeted KO | Progressive hearing loss | Suzuki et al., 2005 |
| TECTA | DFNA8, DFNA12, DFNB21 | Tecta | Targeted KO; Targeted missense |
Inner ears were less sensitive to sound stimulation |
Legan et al., 2000; Legan et al., 2005 |
| SLC26A5 | DFNB61 | Slc26a5 | Targeted KO | Deafness |
Liberman et al., 2002; Cheatham et al., 2004; Wu et al., 2004 |
| MYO7A | DFNB2, DFNA11; USH1B | Myo7a | shaker 1, sh1 | Deafness, hyperactivity, head tossing, and circling behavior |
Gibson et al., 1995 |
| MYO15 | DFNB3 | Myo15 | shaker 2, sh2 | Profound deafness, hyperactivity, head tossing, and circling behavior |
Probst et al., 1998 |
| MYO6 | DFNA22, DFNB37 | Myo6 | snell’s waltzer, sv | Deafness, hyperactivity, head tossing, and circling behavior |
Avraham et al., 1995 |
| SOX2 | Sox2 | Light coat and circling, Lcc; Yellow submarine, Ysb | Complete deafness and circling behavior |
Dong et al., 2002; Kiernan et al., 2005 |
|
| POU4F3/BRN3C | DFNA15 | Pou4f3/Brn3c | Dreidel, ddl; Targeted KO | Profound deafness, hyperactivity, head tossing, and circling behavior |
Erkman et al., 1996; Xiang et al., 1997 |
| NDP | ND: Norrie disease | Ndph | Targeted KO | Blindness, progressive hearing loss beginning at 3 months of age, leading to profound deafness. |
Rehm et al., 2002 |
| ACTG1 | DFNA20, DFNA26 | Actg1 | Targeted KO | Progressive hearing loss | Belyantseva et al., 2009 |
| COCH | DFNA9 | Coch | Targeted missense, late onset hearing loss |
Late-onset, progressive NSSNHL and vestibular dysfunction |
Makishima et al., 2005; Robertson et al., 2008 |
| TMPRSS3 | DFNB10, DFNB8 | Tmprss3 | Targeted KO | Severe deafness and mild vestibular syndrome |
Fasquelle et al., 2011 |
| EYA1 | BOR: branchio-oto-renal syndrome |
Eya1 | Spontaneous—Eya1 bor
Targeted KO |
Complete deafness, circling, head-bobbing behavior, and missing kidneys |
Johnson et al., 1999; Xu et al., 1999 |
| ESPN | DFNB36 | Espn | Jerker, je | Totally deaf from P12d onward, hyperactivity, circling movements, and head tossing |
Zheng et al., 2000b |
| GATA3 | HDR syndrome: hypoparathyroidism, sensorineural deafness, and renal dysplasia |
Gata3 | Targeted KO | Deafness and vestibular dysfunction | Karis et al., 2001 |
| Pax2 | Renal-coloboma syndrome | Pax2 | Targeted KO | Deafness and blindness | Torres et al., 1996 |
TM, tectorial membrane; OHC, outer hair cell; IHC, inner hair cell; SGN, spiral ganglion neuron; NSSNHL, nonsyndromic sensorineural hearing loss.