title: Pou3f4 deficiency causes defects in otic fibrocytes and stria vascularis by different mechanisms.
abstract: DFN3, the most prevalent X-linked hearing loss, is caused by mutations in the POU3F4 gene. Previous studies in Pou3f4 knockout mice suggest that defective otic fibrocytes in the spiral ligament of the cochlear lateral wall may underlie the hearing loss in DFN3. To better understand the pathological mechanisms of the DFN3 hearing loss, we analyzed inner ears of Pou3f4-deficient mice during development. Our results indicate that compartmentalization of the spiral ligament mesenchyme setting up boundaries for specific otic fibrocytes occurs normally in Pou3f4-deficient cochlea. However, differentiation of the compartmentalized mesenchyme into specific otic fibrocytes was blocked in the absence of Pou3f4 function. In addition, we found that stria vascularis in the cochlear lateral wall was also affected in Pou3f4-deficient cochlea. Unlike the otic fibrocytes, differentiation of stria vascularis was completed in the absence of Pou3f4 function, yet expression of Kir4.1 channels in the strial intermediate cells, essential for the sound transduction, was lost afterwards. These results suggest that Pou3f4 deficiency causes defects in both otic fibrocytes and stria vascularis at different developmental stages and by different pathological mechanisms, which may account for the progressive nature of DFN3 hearing loss.
authors.affiliation: Department of Otorhinolaryngology, Kwandong University College of Medicine, Goyang 412-270, South Korea.
authors.forename: Mee Hyun
authors.initials: MH
authors.lastname: Song
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.forename: Se-Kyoung
authors.initials: SK
authors.lastname: Oh
authors.forename: Hee Keun
authors.initials: HK
authors.lastname: Lee
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Lee
authors.forename: Dae-Bo
authors.initials: DB
authors.lastname: Shim
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Bok
mesh_terms: D000818:Animals; D003459:Crystallins / Q000235:genetics; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000002:abnormalities* / Q000473:pathology*; D015870:Gene Expression; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050809:POU Domain Factors / Q000235:genetics*; D055493:Spiral Ligament of Cochlea / Q000196:embryology / Q000473:pathology; D013316:Stria Vascularis / Q000473:pathology*; D000090803:mu-Crystallins
chemical_list: D003459:Crystallins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C074067:Pou3f4 protein, mouse; D000090803:mu-Crystallins