Phenotypic Mutation 'hersey' (pdf version)
Allele | hersey |
Mutation Type |
missense
|
Chromosome | 10 |
Coordinate | 60,143,815 bp (GRCm39) |
Base Change | A ⇒ T (forward strand) |
Gene |
Cdh23
|
Gene Name | cadherin related 23 (otocadherin) |
Synonym(s) | bob, sals, USH1D, ahl, mdfw, nmf252, 4930542A03Rik, nmf112, nmf181 |
Chromosomal Location |
60,138,527-60,532,269 bp (-) (GRCm39)
|
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013] PHENOTYPE: Mutant mice exhibit circling behavior, tilting of the head and are deaf. Mice homozygous for a targeted knock-out exhibit abnormal outer hair cells morphology. [provided by MGI curators]
|
Accession Number | NCBI RefSeq: NM_023370, NM_001252635; MGI:105128
|
Mapped | Yes |
Amino Acid Change |
Valine changed to Glutamic Acid
|
Institutional Source | Beutler Lab |
Gene Model |
predicted gene model for protein(s):
[ENSMUSP00000072973]
[ENSMUSP00000101101]
[ENSMUSP00000101102]
[ENSMUSP00000101103]
[ENSMUSP00000101104]
|
AlphaFold |
no structure available at present |
SMART Domains |
Protein: ENSMUSP00000072973 Gene: ENSMUSG00000012819 AA Change: V2929E
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
23 |
N/A |
INTRINSIC |
CA
|
55 |
130 |
5.15e-13 |
SMART |
CA
|
154 |
234 |
3.19e-18 |
SMART |
CA
|
258 |
346 |
2.03e-11 |
SMART |
CA
|
371 |
458 |
8.11e-11 |
SMART |
CA
|
482 |
559 |
1.04e-22 |
SMART |
CA
|
583 |
669 |
3.55e-25 |
SMART |
CA
|
693 |
776 |
2.04e-25 |
SMART |
CA
|
800 |
888 |
5.03e-16 |
SMART |
CA
|
912 |
993 |
1.05e-27 |
SMART |
CA
|
1017 |
1100 |
1.99e-19 |
SMART |
CA
|
1124 |
1206 |
6.94e-19 |
SMART |
CA
|
1231 |
1311 |
1.99e-19 |
SMART |
CA
|
1335 |
1415 |
1.21e-18 |
SMART |
CA
|
1440 |
1524 |
2.38e-26 |
SMART |
CA
|
1549 |
1631 |
6.27e-26 |
SMART |
CA
|
1656 |
1741 |
6.99e-24 |
SMART |
CA
|
1765 |
1848 |
3.49e-24 |
SMART |
CA
|
1872 |
1956 |
2.78e-18 |
SMART |
CA
|
1984 |
2066 |
5.6e-14 |
SMART |
CA
|
2090 |
2171 |
2.59e-27 |
SMART |
CA
|
2195 |
2290 |
2.87e-11 |
SMART |
CA
|
2317 |
2399 |
1.01e-20 |
SMART |
CA
|
2423 |
2506 |
1.09e-25 |
SMART |
CA
|
2530 |
2608 |
7.91e-23 |
SMART |
CA
|
2634 |
2719 |
1.06e-23 |
SMART |
CA
|
2750 |
2843 |
2e-10 |
SMART |
Blast:CA
|
2867 |
2956 |
4e-51 |
BLAST |
transmembrane domain
|
3067 |
3089 |
N/A |
INTRINSIC |
|
Predicted Effect |
possibly damaging
PolyPhen 2
Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)
(Using ENSMUST00000073242)
|
SMART Domains |
Protein: ENSMUSP00000101101 Gene: ENSMUSG00000012819 AA Change: V2930E
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
23 |
N/A |
INTRINSIC |
CA
|
55 |
130 |
5.15e-13 |
SMART |
CA
|
154 |
234 |
3.19e-18 |
SMART |
CA
|
258 |
346 |
2.03e-11 |
SMART |
CA
|
371 |
458 |
1.25e-11 |
SMART |
CA
|
482 |
559 |
1.04e-22 |
SMART |
CA
|
583 |
669 |
3.55e-25 |
SMART |
CA
|
693 |
776 |
2.04e-25 |
SMART |
CA
|
800 |
888 |
5.03e-16 |
SMART |
CA
|
912 |
993 |
1.05e-27 |
SMART |
CA
|
1017 |
1100 |
1.99e-19 |
SMART |
CA
|
1124 |
1206 |
6.94e-19 |
SMART |
CA
|
1231 |
1311 |
1.99e-19 |
SMART |
CA
|
1335 |
1416 |
5.26e-19 |
SMART |
CA
|
1441 |
1525 |
2.38e-26 |
SMART |
CA
|
1550 |
1632 |
6.27e-26 |
SMART |
CA
|
1657 |
1742 |
6.99e-24 |
SMART |
CA
|
1766 |
1849 |
3.49e-24 |
SMART |
CA
|
1873 |
1957 |
2.78e-18 |
SMART |
CA
|
1985 |
2067 |
5.6e-14 |
SMART |
CA
|
2091 |
2172 |
2.59e-27 |
SMART |
CA
|
2196 |
2291 |
2.87e-11 |
SMART |
CA
|
2318 |
2400 |
1.01e-20 |
SMART |
CA
|
2424 |
2507 |
1.09e-25 |
SMART |
CA
|
2531 |
2609 |
7.91e-23 |
SMART |
CA
|
2635 |
2720 |
1.06e-23 |
SMART |
CA
|
2751 |
2844 |
2e-10 |
SMART |
Blast:CA
|
2868 |
2957 |
4e-51 |
BLAST |
transmembrane domain
|
3068 |
3090 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably damaging
PolyPhen 2
Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)
(Using ENSMUST00000105461)
|
SMART Domains |
Protein: ENSMUSP00000101102 Gene: ENSMUSG00000012819 AA Change: V2932E
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
23 |
N/A |
INTRINSIC |
CA
|
55 |
130 |
5.15e-13 |
SMART |
CA
|
154 |
234 |
3.19e-18 |
SMART |
CA
|
261 |
349 |
2.03e-11 |
SMART |
CA
|
374 |
461 |
8.11e-11 |
SMART |
CA
|
485 |
562 |
1.04e-22 |
SMART |
CA
|
586 |
672 |
3.55e-25 |
SMART |
CA
|
696 |
779 |
2.04e-25 |
SMART |
CA
|
803 |
891 |
5.03e-16 |
SMART |
CA
|
915 |
996 |
1.05e-27 |
SMART |
CA
|
1020 |
1103 |
1.99e-19 |
SMART |
CA
|
1127 |
1209 |
6.94e-19 |
SMART |
CA
|
1234 |
1314 |
1.99e-19 |
SMART |
CA
|
1338 |
1418 |
1.21e-18 |
SMART |
CA
|
1443 |
1527 |
2.38e-26 |
SMART |
CA
|
1552 |
1634 |
6.27e-26 |
SMART |
CA
|
1659 |
1744 |
6.99e-24 |
SMART |
CA
|
1768 |
1851 |
3.49e-24 |
SMART |
CA
|
1875 |
1959 |
2.78e-18 |
SMART |
CA
|
1987 |
2069 |
5.6e-14 |
SMART |
CA
|
2093 |
2174 |
2.59e-27 |
SMART |
CA
|
2198 |
2293 |
2.87e-11 |
SMART |
CA
|
2320 |
2402 |
1.01e-20 |
SMART |
CA
|
2426 |
2509 |
1.09e-25 |
SMART |
CA
|
2533 |
2611 |
7.91e-23 |
SMART |
CA
|
2637 |
2722 |
1.06e-23 |
SMART |
CA
|
2753 |
2846 |
2e-10 |
SMART |
Blast:CA
|
2870 |
2959 |
4e-51 |
BLAST |
transmembrane domain
|
3070 |
3092 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably damaging
PolyPhen 2
Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
(Using ENSMUST00000105462)
|
SMART Domains |
Protein: ENSMUSP00000101103 Gene: ENSMUSG00000012819 AA Change: V2930E
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
23 |
N/A |
INTRINSIC |
CA
|
55 |
130 |
5.15e-13 |
SMART |
CA
|
154 |
234 |
3.19e-18 |
SMART |
CA
|
258 |
346 |
2.03e-11 |
SMART |
CA
|
371 |
458 |
1.25e-11 |
SMART |
CA
|
482 |
559 |
1.04e-22 |
SMART |
CA
|
583 |
669 |
3.55e-25 |
SMART |
CA
|
693 |
776 |
2.04e-25 |
SMART |
CA
|
800 |
888 |
5.03e-16 |
SMART |
CA
|
912 |
993 |
1.05e-27 |
SMART |
CA
|
1017 |
1100 |
1.99e-19 |
SMART |
CA
|
1124 |
1206 |
6.94e-19 |
SMART |
CA
|
1231 |
1311 |
1.99e-19 |
SMART |
CA
|
1335 |
1416 |
5.26e-19 |
SMART |
CA
|
1441 |
1525 |
2.38e-26 |
SMART |
CA
|
1550 |
1632 |
6.27e-26 |
SMART |
CA
|
1657 |
1742 |
6.99e-24 |
SMART |
CA
|
1766 |
1849 |
3.49e-24 |
SMART |
CA
|
1873 |
1957 |
2.78e-18 |
SMART |
CA
|
1985 |
2067 |
5.6e-14 |
SMART |
CA
|
2091 |
2172 |
2.59e-27 |
SMART |
CA
|
2196 |
2291 |
2.87e-11 |
SMART |
CA
|
2318 |
2400 |
1.01e-20 |
SMART |
CA
|
2424 |
2507 |
1.09e-25 |
SMART |
CA
|
2531 |
2609 |
7.91e-23 |
SMART |
CA
|
2635 |
2720 |
1.06e-23 |
SMART |
CA
|
2751 |
2844 |
2e-10 |
SMART |
Blast:CA
|
2868 |
2957 |
4e-51 |
BLAST |
transmembrane domain
|
3068 |
3090 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably damaging
PolyPhen 2
Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)
(Using ENSMUST00000105463)
|
SMART Domains |
Protein: ENSMUSP00000101104 Gene: ENSMUSG00000012819 AA Change: V2928E
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
23 |
N/A |
INTRINSIC |
CA
|
55 |
130 |
5.15e-13 |
SMART |
CA
|
154 |
234 |
3.19e-18 |
SMART |
CA
|
258 |
346 |
2.03e-11 |
SMART |
CA
|
371 |
456 |
3.58e-12 |
SMART |
CA
|
480 |
557 |
1.04e-22 |
SMART |
CA
|
581 |
667 |
3.55e-25 |
SMART |
CA
|
691 |
774 |
2.04e-25 |
SMART |
CA
|
798 |
886 |
5.03e-16 |
SMART |
CA
|
910 |
991 |
1.05e-27 |
SMART |
CA
|
1015 |
1098 |
1.99e-19 |
SMART |
CA
|
1122 |
1204 |
6.94e-19 |
SMART |
CA
|
1229 |
1309 |
1.99e-19 |
SMART |
CA
|
1333 |
1414 |
5.26e-19 |
SMART |
CA
|
1439 |
1523 |
2.38e-26 |
SMART |
CA
|
1548 |
1630 |
6.27e-26 |
SMART |
CA
|
1655 |
1740 |
6.99e-24 |
SMART |
CA
|
1764 |
1847 |
3.49e-24 |
SMART |
CA
|
1871 |
1955 |
2.78e-18 |
SMART |
CA
|
1983 |
2065 |
5.6e-14 |
SMART |
CA
|
2089 |
2170 |
2.59e-27 |
SMART |
CA
|
2194 |
2289 |
2.87e-11 |
SMART |
CA
|
2316 |
2398 |
1.01e-20 |
SMART |
CA
|
2422 |
2505 |
1.09e-25 |
SMART |
CA
|
2529 |
2607 |
7.91e-23 |
SMART |
CA
|
2633 |
2718 |
1.06e-23 |
SMART |
CA
|
2749 |
2842 |
2e-10 |
SMART |
Blast:CA
|
2866 |
2955 |
3e-51 |
BLAST |
transmembrane domain
|
3066 |
3088 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably damaging
PolyPhen 2
Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
(Using ENSMUST00000105464)
|
Meta Mutation Damage Score |
0.8045 |
Is this an essential gene? |
Possibly nonessential (E-score: 0.428) |
Phenotypic Category |
Unknown |
Candidate Explorer Status |
loading ... |
Single pedigree Linkage Analysis Data
|
|
Penetrance | |
Alleles Listed at MGI | All Mutations and Alleles(41) : Chemically induced (ENU)(7) Chemically induced (other)(2) Endonuclease-mediated(3) Gene trapped(2) QTL(2) Radiation induced(1) Spontaneous(13) Targeted(11)
|
Lab Alleles |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00229:Cdh23
|
APN |
10 |
60359327 |
missense |
probably benign |
0.03 |
IGL00429:Cdh23
|
APN |
10 |
60256920 |
missense |
probably damaging |
0.97 |
IGL01014:Cdh23
|
APN |
10 |
60143301 |
missense |
probably damaging |
0.99 |
IGL01284:Cdh23
|
APN |
10 |
60301876 |
missense |
possibly damaging |
0.95 |
IGL01305:Cdh23
|
APN |
10 |
60148403 |
missense |
probably damaging |
1.00 |
IGL01367:Cdh23
|
APN |
10 |
60146566 |
missense |
probably damaging |
1.00 |
IGL01396:Cdh23
|
APN |
10 |
60220848 |
missense |
possibly damaging |
0.93 |
IGL01412:Cdh23
|
APN |
10 |
60150473 |
missense |
probably damaging |
1.00 |
IGL01461:Cdh23
|
APN |
10 |
60244926 |
missense |
possibly damaging |
0.53 |
IGL01469:Cdh23
|
APN |
10 |
60433504 |
missense |
probably benign |
0.03 |
IGL01695:Cdh23
|
APN |
10 |
60167612 |
missense |
probably benign |
0.20 |
IGL01734:Cdh23
|
APN |
10 |
60139292 |
missense |
probably benign |
|
IGL01767:Cdh23
|
APN |
10 |
60151503 |
missense |
probably damaging |
1.00 |
IGL01796:Cdh23
|
APN |
10 |
60146916 |
missense |
probably benign |
0.31 |
IGL01843:Cdh23
|
APN |
10 |
60255598 |
splice site |
probably null |
|
IGL02025:Cdh23
|
APN |
10 |
60220922 |
missense |
probably damaging |
1.00 |
IGL02071:Cdh23
|
APN |
10 |
60359339 |
missense |
possibly damaging |
0.93 |
IGL02160:Cdh23
|
APN |
10 |
60433544 |
splice site |
probably benign |
|
IGL02175:Cdh23
|
APN |
10 |
60167087 |
missense |
possibly damaging |
0.92 |
IGL02220:Cdh23
|
APN |
10 |
60140903 |
missense |
probably damaging |
1.00 |
IGL02302:Cdh23
|
APN |
10 |
60159302 |
missense |
possibly damaging |
0.87 |
IGL02331:Cdh23
|
APN |
10 |
60301322 |
missense |
probably damaging |
0.99 |
IGL02452:Cdh23
|
APN |
10 |
60153721 |
missense |
probably damaging |
0.99 |
IGL02499:Cdh23
|
APN |
10 |
60220958 |
missense |
probably damaging |
1.00 |
IGL02548:Cdh23
|
APN |
10 |
60485901 |
missense |
probably benign |
0.37 |
IGL02593:Cdh23
|
APN |
10 |
60301774 |
splice site |
probably benign |
|
IGL02626:Cdh23
|
APN |
10 |
60227580 |
missense |
probably damaging |
1.00 |
IGL02951:Cdh23
|
APN |
10 |
60147143 |
missense |
probably damaging |
1.00 |
IGL03145:Cdh23
|
APN |
10 |
60212593 |
missense |
probably damaging |
0.99 |
dee_dee
|
UTSW |
10 |
60143835 |
nonsense |
probably null |
|
ANU22:Cdh23
|
UTSW |
10 |
60148403 |
missense |
probably damaging |
1.00 |
IGL02980:Cdh23
|
UTSW |
10 |
60150399 |
missense |
probably damaging |
1.00 |
PIT4362001:Cdh23
|
UTSW |
10 |
60301237 |
missense |
probably benign |
0.15 |
R0013:Cdh23
|
UTSW |
10 |
60248952 |
missense |
possibly damaging |
0.90 |
R0045:Cdh23
|
UTSW |
10 |
60366757 |
missense |
probably damaging |
1.00 |
R0045:Cdh23
|
UTSW |
10 |
60366757 |
missense |
probably damaging |
1.00 |
R0082:Cdh23
|
UTSW |
10 |
60148366 |
missense |
probably damaging |
1.00 |
R0124:Cdh23
|
UTSW |
10 |
60143835 |
nonsense |
probably null |
|
R0172:Cdh23
|
UTSW |
10 |
60155411 |
missense |
probably damaging |
1.00 |
R0195:Cdh23
|
UTSW |
10 |
60152838 |
missense |
probably damaging |
0.99 |
R0365:Cdh23
|
UTSW |
10 |
60215094 |
missense |
probably damaging |
0.99 |
R0437:Cdh23
|
UTSW |
10 |
60246576 |
missense |
probably damaging |
1.00 |
R0486:Cdh23
|
UTSW |
10 |
60222725 |
missense |
probably damaging |
1.00 |
R0494:Cdh23
|
UTSW |
10 |
60152375 |
splice site |
probably benign |
|
R0545:Cdh23
|
UTSW |
10 |
60167070 |
missense |
probably benign |
0.06 |
R0619:Cdh23
|
UTSW |
10 |
60269556 |
missense |
probably damaging |
1.00 |
R0647:Cdh23
|
UTSW |
10 |
60159153 |
nonsense |
probably null |
|
R0647:Cdh23
|
UTSW |
10 |
60143681 |
missense |
probably damaging |
0.99 |
R0730:Cdh23
|
UTSW |
10 |
60159493 |
missense |
probably damaging |
0.99 |
R0880:Cdh23
|
UTSW |
10 |
60242200 |
missense |
possibly damaging |
0.51 |
R0942:Cdh23
|
UTSW |
10 |
60246639 |
missense |
possibly damaging |
0.67 |
R0989:Cdh23
|
UTSW |
10 |
60370289 |
missense |
probably damaging |
0.99 |
R1017:Cdh23
|
UTSW |
10 |
60167572 |
missense |
probably damaging |
1.00 |
R1173:Cdh23
|
UTSW |
10 |
60148171 |
splice site |
probably benign |
|
R1449:Cdh23
|
UTSW |
10 |
60212730 |
missense |
probably damaging |
1.00 |
R1456:Cdh23
|
UTSW |
10 |
60322899 |
missense |
possibly damaging |
0.84 |
R1519:Cdh23
|
UTSW |
10 |
60215122 |
missense |
possibly damaging |
0.92 |
R1532:Cdh23
|
UTSW |
10 |
60150110 |
missense |
probably damaging |
0.99 |
R1559:Cdh23
|
UTSW |
10 |
60255478 |
splice site |
probably benign |
|
R1704:Cdh23
|
UTSW |
10 |
60150390 |
missense |
probably damaging |
1.00 |
R1711:Cdh23
|
UTSW |
10 |
60359315 |
missense |
probably benign |
0.07 |
R1760:Cdh23
|
UTSW |
10 |
60161855 |
missense |
probably damaging |
1.00 |
R1782:Cdh23
|
UTSW |
10 |
60324321 |
missense |
probably damaging |
1.00 |
R1791:Cdh23
|
UTSW |
10 |
60227505 |
missense |
possibly damaging |
0.89 |
R1803:Cdh23
|
UTSW |
10 |
60167060 |
missense |
probably damaging |
1.00 |
R1857:Cdh23
|
UTSW |
10 |
60159076 |
missense |
probably damaging |
1.00 |
R1874:Cdh23
|
UTSW |
10 |
60272597 |
missense |
possibly damaging |
0.52 |
R1914:Cdh23
|
UTSW |
10 |
60159349 |
missense |
probably damaging |
0.99 |
R1958:Cdh23
|
UTSW |
10 |
60246652 |
missense |
probably benign |
0.02 |
R1964:Cdh23
|
UTSW |
10 |
60221001 |
missense |
probably benign |
0.31 |
R1966:Cdh23
|
UTSW |
10 |
60159361 |
missense |
probably damaging |
1.00 |
R1981:Cdh23
|
UTSW |
10 |
60214530 |
missense |
probably damaging |
1.00 |
R2010:Cdh23
|
UTSW |
10 |
60150006 |
missense |
probably damaging |
0.99 |
R2036:Cdh23
|
UTSW |
10 |
60301822 |
missense |
possibly damaging |
0.52 |
R2038:Cdh23
|
UTSW |
10 |
60148366 |
missense |
probably damaging |
1.00 |
R2044:Cdh23
|
UTSW |
10 |
60432509 |
missense |
possibly damaging |
0.72 |
R2111:Cdh23
|
UTSW |
10 |
60141362 |
missense |
probably damaging |
0.99 |
R2112:Cdh23
|
UTSW |
10 |
60141362 |
missense |
probably damaging |
0.99 |
R2211:Cdh23
|
UTSW |
10 |
60301783 |
missense |
possibly damaging |
0.92 |
R2261:Cdh23
|
UTSW |
10 |
60152907 |
missense |
probably damaging |
1.00 |
R2262:Cdh23
|
UTSW |
10 |
60152907 |
missense |
probably damaging |
1.00 |
R2306:Cdh23
|
UTSW |
10 |
60159224 |
missense |
probably damaging |
1.00 |
R2344:Cdh23
|
UTSW |
10 |
60152503 |
missense |
probably damaging |
1.00 |
R2857:Cdh23
|
UTSW |
10 |
60218432 |
critical splice donor site |
probably null |
|
R2858:Cdh23
|
UTSW |
10 |
60218432 |
critical splice donor site |
probably null |
|
R2859:Cdh23
|
UTSW |
10 |
60218432 |
critical splice donor site |
probably null |
|
R2876:Cdh23
|
UTSW |
10 |
60143275 |
missense |
probably damaging |
1.00 |
R3034:Cdh23
|
UTSW |
10 |
60244789 |
splice site |
probably benign |
|
R3424:Cdh23
|
UTSW |
10 |
60212660 |
missense |
possibly damaging |
0.76 |
R3699:Cdh23
|
UTSW |
10 |
60163149 |
critical splice donor site |
probably null |
|
R3700:Cdh23
|
UTSW |
10 |
60163149 |
critical splice donor site |
probably null |
|
R3950:Cdh23
|
UTSW |
10 |
60493105 |
missense |
probably benign |
0.04 |
R3951:Cdh23
|
UTSW |
10 |
60493105 |
missense |
probably benign |
0.04 |
R3952:Cdh23
|
UTSW |
10 |
60493105 |
missense |
probably benign |
0.04 |
R4108:Cdh23
|
UTSW |
10 |
60246601 |
missense |
possibly damaging |
0.51 |
R4114:Cdh23
|
UTSW |
10 |
60256819 |
splice site |
probably null |
|
R4273:Cdh23
|
UTSW |
10 |
60146940 |
missense |
possibly damaging |
0.69 |
R4284:Cdh23
|
UTSW |
10 |
60139272 |
missense |
possibly damaging |
0.91 |
R4334:Cdh23
|
UTSW |
10 |
60220838 |
missense |
probably damaging |
0.99 |
R4474:Cdh23
|
UTSW |
10 |
60146865 |
missense |
probably damaging |
1.00 |
R4532:Cdh23
|
UTSW |
10 |
60370202 |
missense |
probably benign |
0.32 |
R4597:Cdh23
|
UTSW |
10 |
60244823 |
missense |
probably damaging |
1.00 |
R4604:Cdh23
|
UTSW |
10 |
60173445 |
missense |
possibly damaging |
0.93 |
R4793:Cdh23
|
UTSW |
10 |
60167129 |
missense |
probably damaging |
1.00 |
R4816:Cdh23
|
UTSW |
10 |
60244856 |
missense |
possibly damaging |
0.93 |
R4833:Cdh23
|
UTSW |
10 |
60220817 |
missense |
probably damaging |
1.00 |
R4840:Cdh23
|
UTSW |
10 |
60255556 |
missense |
possibly damaging |
0.53 |
R4857:Cdh23
|
UTSW |
10 |
60227563 |
missense |
probably damaging |
1.00 |
R4869:Cdh23
|
UTSW |
10 |
60212713 |
missense |
probably damaging |
1.00 |
R4894:Cdh23
|
UTSW |
10 |
60173630 |
missense |
probably benign |
0.04 |
R4940:Cdh23
|
UTSW |
10 |
60143714 |
missense |
probably damaging |
0.98 |
R5020:Cdh23
|
UTSW |
10 |
60143811 |
missense |
probably damaging |
0.99 |
R5026:Cdh23
|
UTSW |
10 |
60140627 |
missense |
possibly damaging |
0.88 |
R5081:Cdh23
|
UTSW |
10 |
60272586 |
missense |
possibly damaging |
0.89 |
R5138:Cdh23
|
UTSW |
10 |
60148061 |
missense |
probably damaging |
1.00 |
R5236:Cdh23
|
UTSW |
10 |
60148351 |
missense |
probably damaging |
1.00 |
R5361:Cdh23
|
UTSW |
10 |
60493044 |
critical splice donor site |
probably null |
|
R5384:Cdh23
|
UTSW |
10 |
60173541 |
missense |
probably damaging |
0.99 |
R5500:Cdh23
|
UTSW |
10 |
60150090 |
missense |
probably damaging |
1.00 |
R5512:Cdh23
|
UTSW |
10 |
60370165 |
splice site |
probably null |
|
R5673:Cdh23
|
UTSW |
10 |
60143636 |
missense |
probably damaging |
1.00 |
R5720:Cdh23
|
UTSW |
10 |
60228802 |
missense |
possibly damaging |
0.71 |
R5726:Cdh23
|
UTSW |
10 |
60243259 |
missense |
probably damaging |
0.98 |
R5732:Cdh23
|
UTSW |
10 |
60167096 |
missense |
possibly damaging |
0.80 |
R5739:Cdh23
|
UTSW |
10 |
60141388 |
missense |
probably damaging |
0.99 |
R5760:Cdh23
|
UTSW |
10 |
60242171 |
missense |
probably damaging |
0.99 |
R5793:Cdh23
|
UTSW |
10 |
60141907 |
missense |
probably damaging |
1.00 |
R5880:Cdh23
|
UTSW |
10 |
60220713 |
missense |
probably damaging |
1.00 |
R5905:Cdh23
|
UTSW |
10 |
60370314 |
missense |
probably damaging |
0.98 |
R5907:Cdh23
|
UTSW |
10 |
60264158 |
missense |
probably damaging |
1.00 |
R5910:Cdh23
|
UTSW |
10 |
60213600 |
missense |
possibly damaging |
0.81 |
R5932:Cdh23
|
UTSW |
10 |
60228763 |
missense |
probably damaging |
1.00 |
R5996:Cdh23
|
UTSW |
10 |
60249356 |
missense |
possibly damaging |
0.85 |
R6015:Cdh23
|
UTSW |
10 |
60143761 |
missense |
probably damaging |
0.97 |
R6020:Cdh23
|
UTSW |
10 |
60167105 |
missense |
probably damaging |
1.00 |
R6023:Cdh23
|
UTSW |
10 |
60301321 |
missense |
probably damaging |
1.00 |
R6028:Cdh23
|
UTSW |
10 |
60370314 |
missense |
probably damaging |
0.98 |
R6066:Cdh23
|
UTSW |
10 |
60269537 |
missense |
probably damaging |
1.00 |
R6137:Cdh23
|
UTSW |
10 |
60270291 |
missense |
probably damaging |
0.96 |
R6211:Cdh23
|
UTSW |
10 |
60246600 |
missense |
possibly damaging |
0.90 |
R6298:Cdh23
|
UTSW |
10 |
60262451 |
nonsense |
probably null |
|
R6302:Cdh23
|
UTSW |
10 |
60140872 |
missense |
possibly damaging |
0.74 |
R6338:Cdh23
|
UTSW |
10 |
60248930 |
missense |
probably damaging |
1.00 |
R6356:Cdh23
|
UTSW |
10 |
60274626 |
missense |
probably damaging |
1.00 |
R6441:Cdh23
|
UTSW |
10 |
60143815 |
missense |
probably damaging |
1.00 |
R6714:Cdh23
|
UTSW |
10 |
60167609 |
missense |
possibly damaging |
0.62 |
R6760:Cdh23
|
UTSW |
10 |
60141947 |
missense |
probably damaging |
1.00 |
R6807:Cdh23
|
UTSW |
10 |
60214650 |
missense |
possibly damaging |
0.95 |
R6855:Cdh23
|
UTSW |
10 |
60141901 |
missense |
possibly damaging |
0.66 |
R6937:Cdh23
|
UTSW |
10 |
60322893 |
missense |
probably damaging |
1.00 |
R6942:Cdh23
|
UTSW |
10 |
60274635 |
missense |
possibly damaging |
0.93 |
R6961:Cdh23
|
UTSW |
10 |
60485893 |
missense |
probably benign |
0.00 |
R7009:Cdh23
|
UTSW |
10 |
60173085 |
missense |
probably damaging |
0.99 |
R7010:Cdh23
|
UTSW |
10 |
60366770 |
missense |
probably benign |
0.03 |
R7032:Cdh23
|
UTSW |
10 |
60167567 |
missense |
probably damaging |
1.00 |
R7046:Cdh23
|
UTSW |
10 |
60214530 |
missense |
probably damaging |
1.00 |
R7111:Cdh23
|
UTSW |
10 |
60222823 |
missense |
probably damaging |
1.00 |
R7196:Cdh23
|
UTSW |
10 |
60143759 |
missense |
probably damaging |
0.99 |
R7198:Cdh23
|
UTSW |
10 |
60148378 |
missense |
possibly damaging |
0.91 |
R7223:Cdh23
|
UTSW |
10 |
60167596 |
missense |
probably damaging |
1.00 |
R7290:Cdh23
|
UTSW |
10 |
60212620 |
missense |
probably benign |
|
R7335:Cdh23
|
UTSW |
10 |
60140895 |
missense |
probably damaging |
1.00 |
R7340:Cdh23
|
UTSW |
10 |
60366775 |
missense |
probably benign |
0.19 |
R7350:Cdh23
|
UTSW |
10 |
60246689 |
missense |
probably damaging |
1.00 |
R7366:Cdh23
|
UTSW |
10 |
60151471 |
nonsense |
probably null |
|
R7374:Cdh23
|
UTSW |
10 |
60153679 |
missense |
probably damaging |
0.99 |
R7455:Cdh23
|
UTSW |
10 |
60142003 |
missense |
possibly damaging |
0.82 |
R7537:Cdh23
|
UTSW |
10 |
60220724 |
missense |
probably benign |
0.17 |
R7573:Cdh23
|
UTSW |
10 |
60159329 |
missense |
probably benign |
0.17 |
R7578:Cdh23
|
UTSW |
10 |
60243186 |
missense |
probably benign |
0.14 |
R7646:Cdh23
|
UTSW |
10 |
60140931 |
missense |
possibly damaging |
0.95 |
R7703:Cdh23
|
UTSW |
10 |
60173043 |
missense |
probably damaging |
1.00 |
R7763:Cdh23
|
UTSW |
10 |
60148356 |
missense |
probably damaging |
1.00 |
R7797:Cdh23
|
UTSW |
10 |
60220973 |
missense |
probably benign |
0.07 |
R7867:Cdh23
|
UTSW |
10 |
60150390 |
missense |
probably damaging |
1.00 |
R7878:Cdh23
|
UTSW |
10 |
60149979 |
missense |
possibly damaging |
0.69 |
R7915:Cdh23
|
UTSW |
10 |
60143668 |
missense |
probably damaging |
0.97 |
R7922:Cdh23
|
UTSW |
10 |
60218485 |
missense |
probably benign |
0.31 |
R7963:Cdh23
|
UTSW |
10 |
60171967 |
missense |
probably damaging |
1.00 |
R7997:Cdh23
|
UTSW |
10 |
60432518 |
missense |
possibly damaging |
0.81 |
R8167:Cdh23
|
UTSW |
10 |
60150162 |
missense |
probably benign |
0.12 |
R8167:Cdh23
|
UTSW |
10 |
60173472 |
missense |
probably damaging |
0.96 |
R8258:Cdh23
|
UTSW |
10 |
60151435 |
missense |
probably damaging |
0.99 |
R8259:Cdh23
|
UTSW |
10 |
60151435 |
missense |
probably damaging |
0.99 |
R8317:Cdh23
|
UTSW |
10 |
60272568 |
missense |
probably damaging |
1.00 |
R8317:Cdh23
|
UTSW |
10 |
60147037 |
critical splice donor site |
probably null |
|
R8326:Cdh23
|
UTSW |
10 |
60274591 |
missense |
possibly damaging |
0.55 |
R8333:Cdh23
|
UTSW |
10 |
60150390 |
missense |
probably damaging |
1.00 |
R8348:Cdh23
|
UTSW |
10 |
60167507 |
missense |
probably benign |
0.43 |
R8366:Cdh23
|
UTSW |
10 |
60160799 |
missense |
probably benign |
|
R8504:Cdh23
|
UTSW |
10 |
60274618 |
missense |
probably benign |
0.00 |
R8676:Cdh23
|
UTSW |
10 |
60246689 |
missense |
probably damaging |
1.00 |
R8781:Cdh23
|
UTSW |
10 |
60167567 |
missense |
probably damaging |
1.00 |
R8785:Cdh23
|
UTSW |
10 |
60147114 |
missense |
probably damaging |
1.00 |
R8788:Cdh23
|
UTSW |
10 |
60324372 |
missense |
probably damaging |
1.00 |
R8802:Cdh23
|
UTSW |
10 |
60244877 |
missense |
probably benign |
0.04 |
R8837:Cdh23
|
UTSW |
10 |
60160755 |
missense |
probably benign |
0.28 |
R8863:Cdh23
|
UTSW |
10 |
60212613 |
nonsense |
probably null |
|
R8889:Cdh23
|
UTSW |
10 |
60143284 |
missense |
probably damaging |
0.97 |
R8892:Cdh23
|
UTSW |
10 |
60143284 |
missense |
probably damaging |
0.97 |
R8921:Cdh23
|
UTSW |
10 |
60140908 |
missense |
probably damaging |
0.99 |
R8980:Cdh23
|
UTSW |
10 |
60173625 |
missense |
probably benign |
0.06 |
R9000:Cdh23
|
UTSW |
10 |
60140277 |
missense |
possibly damaging |
0.82 |
R9043:Cdh23
|
UTSW |
10 |
60151478 |
missense |
probably benign |
0.00 |
R9046:Cdh23
|
UTSW |
10 |
60218303 |
intron |
probably benign |
|
R9070:Cdh23
|
UTSW |
10 |
60173539 |
missense |
probably benign |
|
R9075:Cdh23
|
UTSW |
10 |
60153541 |
missense |
probably damaging |
1.00 |
R9132:Cdh23
|
UTSW |
10 |
60270283 |
splice site |
probably benign |
|
R9155:Cdh23
|
UTSW |
10 |
60249485 |
missense |
probably damaging |
0.99 |
R9171:Cdh23
|
UTSW |
10 |
60161810 |
missense |
probably benign |
0.00 |
R9179:Cdh23
|
UTSW |
10 |
60153664 |
missense |
probably benign |
0.06 |
R9186:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9189:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9207:Cdh23
|
UTSW |
10 |
60243210 |
missense |
probably damaging |
1.00 |
R9240:Cdh23
|
UTSW |
10 |
60215044 |
missense |
probably benign |
0.00 |
R9244:Cdh23
|
UTSW |
10 |
60249442 |
missense |
possibly damaging |
0.93 |
R9284:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9286:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9287:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9302:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9352:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9353:Cdh23
|
UTSW |
10 |
60143306 |
missense |
possibly damaging |
0.54 |
R9423:Cdh23
|
UTSW |
10 |
60148387 |
missense |
probably damaging |
1.00 |
R9513:Cdh23
|
UTSW |
10 |
60166995 |
missense |
probably damaging |
0.99 |
R9577:Cdh23
|
UTSW |
10 |
60146895 |
missense |
probably damaging |
1.00 |
R9598:Cdh23
|
UTSW |
10 |
60214574 |
missense |
probably benign |
0.01 |
R9631:Cdh23
|
UTSW |
10 |
60243168 |
missense |
possibly damaging |
0.49 |
R9652:Cdh23
|
UTSW |
10 |
60167135 |
missense |
probably damaging |
1.00 |
R9725:Cdh23
|
UTSW |
10 |
60432561 |
missense |
probably benign |
0.02 |
X0052:Cdh23
|
UTSW |
10 |
60220913 |
missense |
probably damaging |
1.00 |
Z1088:Cdh23
|
UTSW |
10 |
60249423 |
missense |
probably benign |
0.35 |
Z1176:Cdh23
|
UTSW |
10 |
60264100 |
missense |
probably benign |
|
Z1176:Cdh23
|
UTSW |
10 |
60146549 |
missense |
probably damaging |
1.00 |
Z1177:Cdh23
|
UTSW |
10 |
60270393 |
critical splice acceptor site |
probably null |
|
Z1177:Cdh23
|
UTSW |
10 |
60159334 |
missense |
possibly damaging |
0.80 |
|
Mode of Inheritance |
Unknown |
Local Stock | Live Mice |
Repository | |
Last Updated |
2019-09-04 9:33 PM
by Anne Murray
|
Record Created |
2018-09-18 1:09 PM
by Jamie Russell
|
Record Posted |
2018-10-11 |
Phenotypic Description |
The hersey phenotype was identified among G3 mice of the pedigree R6441, some of which showed circling and abnormal movements (Figure 1). Some mice also showed reduced body weights compared to wild-type littermates (Figure 2).
|
Nature of Mutation |
Whole exome HiSeq sequencing of the G1 grandsire identified 39 mutations. The above anomalies were linked to a mutation in Cdh23: a T to A transversion at base pair 60,308,036 (v38) on chromosome 10, or base pair 388,478 in the GenBank genomic region NC_000076.6. The strongest association was found with a recessive model of inheritance to the behavioral phenotype, wherein six variant homozygotes departed phenotypically from 33 homozygous reference mice and 37 heterozygous mice with a P value of 3.032 x 10-9 (Figure 3). The mutation corresponds to residue 9,196 in the mRNA sequence NM_023370.3 within exon 61 of 70 total exons.
9180 CCTGGCTATTTTGTGGTAGACATCGTGGCCCGA
2923 -P--G--Y--F--V--V--D--I--V--A--R-
|
The mutated nucleotide is indicated in red. The mutation results in a valine to glutamic acid substitution at position 2,928 (V2928E) in the Cdh23 protein, and is strongly predicted by Polyphen-2 to cause loss of function (score = 0.993).
|
Illustration of Mutations in
Gene & Protein |
|
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Protein Prediction |
Cdh23 (alternatively, Ush1d) encodes cadherin 23 (Cdh23), a member of the cadherin superfamily of cell-cell adhesion proteins (1). The cadherin proteins share similar features including a signal peptide (amino acids (aa) 1-23 in Cdh23), an extracellular domain (aa 24-3064 in Cdh23) with a variable number of extracellular ectodomain (EC) repeats (alternatively, cadherin motifs; Cdh23 has 27 EC repeats), a single helical transmembrane domain (aa 3065-3085 in Cdh23), and a cytoplasmic C-terminus (aa 3086-3354 in Cdh23) that connects the cadherin protein to the actin cytoskeleton through interactions with α- and β-catenin (Figure 4; (1-4)). Each Cdh23 EC repeat has four calcium binding motifs that together bind three calcium ions. Cdh23 forms homodimers and heterodimers with protocadherin 15 (Pcdh15; see the record for squirm) through interactions along the full length of the extracellular domain (5;6). Cdh23 interacts with Pcdh15 to form tip links, extracellular filaments that connect the tips of hair cell stereocilia and function in the gating of the hair cell’s mechanotransducer channel (5;7-9). Within the cytoplasmic domain of Cdh23 are two PDZ-binding interfaces (PBIs) that interact with PDZ domains of other proteins. The hersey mutation results in a valine to glutamic acid substitution at position 2,928 (V2928E); Val2928 is within the last EC repeat. For more information about Cdh23, please see the record for dee_dee.
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Putative Mechanism | At their apical surface, hair cells in the cochlea of the inner ear have a single kinocilium and a bundle of actin-filled stereocilia arranged in a staircase of increasing height (10-12). Each stereocilium is connected to its taller neighbor by the tip link (13); side links, ankle links, and horizontal top connectors also connect the individual stereocilia and coordinate their movement (14;15). Cdh23 interacts with Pcdh15 to form the tip link (16-18). During deflection of the hair bundle, the tip link translates the mechanical forces arising from sound waves and head movement into electrochemical signals through gating of the mechanoelectric transducer channels at the lower end of each tip link (11;15;19); these electrical signals facilitate hearing and balance (7). In the synaptic terminals of the photoreceptor cells of the retina, Cdh23 colocalizes with Pcdh15, harmonin, and Myo7a. The complex in the photoreceptor synapse is proposed to have a role in the structural and functional organization of the synaptic junction (20). See the record squirm for more information about the sensory cells in the inner ear and retina as well as the known functions of Cdh23, Pcdh15, and the Usher syndrome-associated proteins therein. In humans, missense mutations in CDH23 are typically linked to autosomal recessive deafness 12 [DFNB12; OMIM: #601386; (3;21)], while null mutations are typically linked to Usher syndrome type 1D (USH1D) and Usher syndrome type 1D/F digenic [OMIM: #601067; (3;4)]. USH1D is characterized by hearing loss, retinitis pigmentosa leading to blindness, and in some cases, vestibular dysfunction (10;18;22). Type 1D/F Usher syndrome is caused by heterozygous mutations in both CDH23 and PCDH15. Patients with Usher syndrome type 1D/F exhibit congenital nonprogressive deafness, vestibular dysfunction, and retinitis pigmentosa (23). Several Cdh23 mutant mouse alleles have been reported and all (with the exception of Cdh23v-bus (MGI:1856681), a donor splice site mutation after exon 67 in Cdh23) are within or affect an EC domain (1;16;18;25-29). Similar to the mutations found in humans, nonsense and splice-site mutations that lead to Cdh23 null alleles result in USHD1 phenotypes, while missense mutations result in phenotypes characteristic of DFNB12 [reviewed in (18)]. The null mutations [e.g., waltzer (Cdh23v; MGI:1856228)] affect hair bundle development and cause defects in the organization of the stereocilial bundle in the cochlear hair cells and misplaced kinocilia (1;28;30). These defects lead to both hearing loss and vestibular defects (as exhibited by circling, head tilt, and/or head tossing) (1;27;28). In contrast, the hair cells and hair bundles develop normally in mouse mutants with missense mutations of Cdh23, but the function is affected (24). Although all of the mouse models exhibit hearing loss; retinal degeneration does not occur (18). Examination of three Cdh23 null mutants using electroretinography determined that two out of the three mutants exhibited abnormal retinal function; cone photoreceptor function was mildly attenuated as well as the response of retinal interneurons (22). However, histological examination determined that the anatomy of the retinas were normal (22). Libby et al. propose that the difference between the mouse and human retina phenotypes in null mutants is dependent on genetic background (22). It is possible that in other genetic backgrounds that have yet to be tested, Cdh23 null alleles may exhibit retinal degeneration. The hersey mice exhibit vestibular dysfunction similar to waltzer and other Cdh23 null mouse models.
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Primers |
PCR Primer
hersey_pcr_F: CAATGGCGCCTGTGATGTTG
hersey_pcr_R: TGTTTACATAAAGCTGGAGCAACC
Sequencing Primer
hersey_seq_F: CCTGTGATGTTGGACAGCAG
hersey_seq_R: AATCAGGAGCGTTTCAGCC
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Genotyping | PCR program 1) 94°C 2:00 2) 94°C 0:30 3) 55°C 0:30 4) 72°C 1:00 5) repeat steps (2-4) 40x 6) 72°C 10:00 7) 4°C hold
The following sequence of 431 nucleotides is amplified (chromosome 10, - strand):
1 tgtttacata aagctggagc aaccactaaa aatcaggagc gtttcagcca ggcatgctag 61 cgtatgccta taatcccagc actcaggctg tggacgtgga gaactctgac ttcctccaag 121 gatgtggctt agggggcagg gcttatcatc agtatgtgtg gcctctgagc tgtgccaccc 181 cgactcttta acagggagtg tggacggtat cctgcgcacc tttgacctct tcatggccta 241 cagccctggc tattttgtgg tagacatcgt ggcccgagac ctggccggcc acaatgatac 301 cgccatcatc ggcatctaca tcctgaggga tgaccagcgc gtgaagatcg tcatcaatga 361 gatcccggac cgcgtgcgtg gcttcgagga ggagttcatt cgcctgctgt ccaacatcac 421 aggcgccatt g
Primer binding sites are underlined and the sequencing primers are highlighted; the mutated nucleotide is shown in red. |
References | 1. Di Palma, F., Holme, R. H., Bryda, E. C., Belyantseva, I. A., Pellegrino, R., Kachar, B., Steel, K. P., and Noben-Trauth, K. (2001) Mutations in Cdh23, Encoding a New Type of Cadherin, Cause Stereocilia Disorganization in Waltzer, the Mouse Model for Usher Syndrome Type 1D. Nat Genet. 27, 103-107.
3. Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R., Wayne, S., Bellman, S., Desmukh, D., Ahmed, Z., Khan, S. N., Kaloustian, V. M., Li, X. C., Lalwani, A., Riazuddin, S., Bitner-Glindzicz, M., Nance, W. E., Liu, X. Z., Wistow, G., Smith, R. J., Griffith, A. J., Wilcox, E. R., Friedman, T. B., and Morell, R. J. (2001) Usher Syndrome 1D and Nonsyndromic Autosomal Recessive Deafness DFNB12 are Caused by Allelic Mutations of the Novel Cadherin-Like Gene CDH23. Am J Hum Genet. 68, 26-37.
4. Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., del C-Salcedo Cabrera, M., Vila, M. C., Molina, O. P., Gal, A., and Kubisch, C. (2001) Mutation of CDH23, Encoding a New Member of the Cadherin Gene Family, Causes Usher Syndrome Type 1D. Nat Genet. 27, 108-112.
5 Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., and Kachar, B. (2007) Cadherin 23 and Protocadherin 15 Interact to Form Tip-Link Filaments in Sensory Hair Cells. Nature. 449, 87-91.
8. Lelli, A., Kazmierczak, P., Kawashima, Y., Muller, U., and Holt, J. R. (2010) Development and Regeneration of Sensory Transduction in Auditory Hair Cells Requires Functional Interaction between Cadherin-23 and Protocadherin-15. J Neurosci. 30, 11259-11269.
9. Alagramam, K. N., Goodyear, R. J., Geng, R., Furness, D. N., van Aken, A. F., Marcotti, W., Kros, C. J., and Richardson, G. P. (2011) Mutations in Protocadherin 15 and Cadherin 23 Affect Tip Links and Mechanotransduction in Mammalian Sensory Hair Cells. PLoS One. 6, e19183.
10. Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., and Petit, C. (2002) Myosin VIIa, Harmonin and Cadherin 23, Three Usher I Gene Products that Cooperate to Shape the Sensory Hair Cell Bundle. EMBO J. 21, 6689-6699.
11. Bahloul, A., Michel, V., Hardelin, J. P., Nouaille, S., Hoos, S., Houdusse, A., England, P., and Petit, C. (2010) Cadherin-23, Myosin VIIa and Harmonin, Encoded by Usher Syndrome Type I Genes, Form a Ternary Complex and Interact with Membrane Phospholipids. Hum Mol Genet. 19, 3557-3565.
13. Kachar, B., Parakkal, M., Kurc, M., Zhao, Y., and Gillespie, P. G. (2000) High-Resolution Structure of Hair-Cell Tip Links. Proc Natl Acad Sci U S A. 97, 13336-13341.
18. Manji, S. S., Miller, K. A., Williams, L. H., Andreasen, L., Siboe, M., Rose, E., Bahlo, M., Kuiper, M., and Dahl, H. H. (2011) An ENU-Induced Mutation of Cdh23 Causes Congenital Hearing Loss, but no Vestibular Dysfunction, in Mice. Am J Pathol. 179, 903-914.
19. Xu, Z., Peng, A. W., Oshima, K., and Heller, S. (2008) MAGI-1, a Candidate Stereociliary Scaffolding Protein, Associates with the Tip-Link Component Cadherin 23. J Neurosci. 28, 11269-11276.
20. Reiners, J., Marker, T., Jurgens, K., Reidel, B., and Wolfrum, U. (2005) Photoreceptor Expression of the Usher Syndrome Type 1 Protein Protocadherin 15 (USH1F) and its Interaction with the Scaffold Protein Harmonin (USH1C). Mol Vis. 11, 347-355.
div> 21. Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., and Usami, S. (2007) Distribution and Frequencies of CDH23 Mutations in Japanese Patients with Non-Syndromic Hearing Loss. Clin Genet. 72, 339-344.
22. Libby, R. T., Kitamoto, J., Holme, R. H., Williams, D. S., and Steel, K. P. (2003) Cdh23 Mutations in the Mouse are Associated with Retinal Dysfunction but Not Retinal Degeneration. Exp Eye Res. 77, 731-739.
23. Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., and Liu, X. Z. (2005) Digenic Inheritance of Deafness Caused by Mutations in Genes Encoding Cadherin 23 and Protocadherin 15 in Mice and Humans. Hum Mol Genet. 14, 103-111.
24. Schwander, M., Xiong, W., Tokita, J., Lelli, A., Elledge, H. M., Kazmierczak, P., Sczaniecka, A., Kolatkar, A., Wiltshire, T., Kuhn, P., Holt, J. R., Kachar, B., Tarantino, L., and Muller, U. (2009) A Mouse Model for Nonsyndromic Deafness (DFNB12) Links Hearing Loss to Defects in Tip Links of Mechanosensory Hair Cells. Proc Natl Acad Sci U S A. 106, 5252-5257.
25. Wilson, S. M., Householder, D. B., Coppola, V., Tessarollo, L., Fritzsch, B., Lee, E. C., Goss, D., Carlson, G. A., Copeland, N. G., and Jenkins, N. A. (2001) Mutations in Cdh23 Cause Nonsyndromic Hearing Loss in Waltzer Mice. Genomics. 74, 228-233.
27. Yonezawa, S., Yoshizaki, N., Kageyama, T., Takahashi, T., Sano, M., Tokita, Y., Masaki, S., Inaguma, Y., Hanai, A., Sakurai, N., Yoshiki, A., Kusakabe, M., Moriyama, A., and Nakayama, A. (2006) Fates of Cdh23/CDH23 with Mutations Affecting the Cytoplasmic Region. Hum Mutat. 27, 88-97.
28. Wada, T., Wakabayashi, Y., Takahashi, S., Ushiki, T., Kikkawa, Y., Yonekawa, H., and Kominami, R. (2001) A Point Mutation in a Cadherin Gene, Cdh23, Causes Deafness in a Novel Mutant, Waltzer Mouse Niigata. Biochem Biophys Res Commun. 283, 113-117.
29. Han, F., Yu, H., Tian, C., Chen, H. E., Benedict-Alderfer, C., Zheng, Y., Wang, Q., Han, X., and Zheng, Q. Y. (2012) A New Mouse Mutant of the Cdh23 Gene with Early-Onset Hearing Loss Facilitates Evaluation of Otoprotection Drugs. Pharmacogenomics J. 12, 30-44.
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Science Writers | Anne Murray |
Authors | Lauren Prince, Jamie Russell, and Bruce Beutler |