Distribution of type IV collagen in the cochlea in Alport syndrome.
OBJECTIVE
To determine the distribution of alpha1, alpha3, and alpha5 chains of type IV collagen in the cochlea in Alport syndrome.


METHODS
Case-control study.


METHODS
Two patients with sensorineural hearing loss due to Alport syndrome. Both patients had known mutations in the COL4A5 gene.


METHODS
Immunostaining was used to study the distribution of type IV collagen (alpha1, alpha3, and alpha5 chains) within the cochlea. Immunostaining was also performed in the cochlear tissues of an unaffected individual used as a control.


RESULTS
In the control ear, alpha1 staining was observed in the basement membrane overlying the basilar membrane, in the basement membrane of cochlear blood vessels and Schwann cells, and within the spiral limbus. In the control ear, we also observed strong staining for alpha3 and alpha5 chains in the basement membrane overlying the basilar membrane and within the spiral ligament. In both cases with Alport syndrome, no immunostaining was observed for alpha3 or alpha5 chains within the cochlea, whereas alpha1 staining was present in locations similar to that seen in the control ear.


CONCLUSIONS
The results indicate that isotype switching does not occur within the cochlea in Alport syndrome. The results are also consistent with the hypothesis that the sensorineural hearing loss in Alport syndrome may be due to alterations in cochlear micromechanics and/or dysfunction of the spiral ligament.
Zehnder
Andreas F
AF
Ear, Nose, and Throat Department, University Hospital Basel, Basel, Switzerland.
Adams
Joe C
JC
Santi
Peter A
PA
Kristiansen
Arthur G
AG
Wacharasindhu
Chitsuda
C
Mann
Sabine
S
Kalluri
Raghu
R
Gregory
Martin C
MC
Kashtan
Clifford E
CE
Merchant
Saumil N
SN
D000328:Adult; D001485:Basement Membrane / Q000378:metabolism; D016022:Case-Control Studies; D003051:Cochlea / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D005260:Female; D005456:Fluorescent Dyes; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000378:metabolism; D006416:Hematoxylin; D006801:Humans; D008297:Male; D008859:Microscopy, Polarization; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009394:Nephritis, Hereditary / Q000150:complications / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism
C478159:COL4A5 protein, human; D024141:Collagen Type IV; D004396:Coloring Agents; D005456:Fluorescent Dyes; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin