title: The role of Pax2 in mouse inner ear development.
abstract: The paired box transcription factor, Pax2, is important for cochlear development in the mouse inner ear. Two mutant alleles of Pax2, a knockout and a frameshift mutation (Pax21Neu), show either agenesis or severe malformation of the cochlea, respectively. In humans, mutations in the PAX2 gene cause renal coloboma syndrome that is characterized by kidney abnormalities, optic nerve colobomas and mild sensorineural deafness. To better understand the role of Pax2 in inner ear development, we examined the inner ear phenotype in the Pax2 knockout mice using paint-fill and gene expression analyses. We show that Pax2-/- ears often lack a distinct saccule, and the endolymphatic duct and common crus are invariably fused. However, a rudimentary cochlea is always present in all Pax2 knockout inner ears. Cochlear outgrowth in the mutants is arrested at an early stage due to apoptosis of cells that normally express Pax2 in the cochlear anlage. Lack of Pax2 affects tissue specification within the cochlear duct, particularly regions between the sensory tissue and the stria vascularis. Because the cochlear phenotypes observed in Pax2 mutants are more severe than those observed in mice lacking Otx1 and Otx2, we postulate that Pax2 plays a key role in regulating the differential growth within the cochlear duct and thus, its proper outgrowth and coiling.
authors.affiliation: National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA.
authors.forename: Quianna
authors.initials: Q
authors.lastname: Burton
authors.forename: Laura K
authors.initials: LK
authors.lastname: Cole
authors.forename: Michael
authors.initials: M
authors.lastname: Mulheisen
authors.forename: Weise
authors.initials: W
authors.lastname: Chang
authors.forename: Doris K
authors.initials: DK
authors.lastname: Wu
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D003053:Cochlear Duct / Q000196:embryology / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007758:Ear, Inner / Q000166:cytology / Q000196:embryology* / Q000473:pathology; D004711:Endolymphatic Duct / Q000196:embryology / Q000473:pathology; D050990:GATA3 Transcription Factor; D045888:Ganglion Cysts / Q000235:genetics / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D051857:Otx Transcription Factors; D051762:PAX2 Transcription Factor; D017027:Protein Tyrosine Phosphatases; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029867:Xenopus Proteins
chemical_list: C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051857:Otx Transcription Factors; C497656:Otx1 protein, mouse; C497660:Otx2 protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D016695:Glycosyltransferases; C498393:LFNG protein, human; C498392:Lfng protein, mouse; C501157:Eya1 protein, Xenopus; C501156:Eya1 protein, mouse; D017027:Protein Tyrosine Phosphatases