title: Characterization of neuronal cell death in the spiral ganglia of a mouse model of endolymphatic hydrops.
abstract: OBJECTIVE
  Spiral ganglion neurons (SGN) in the Phex male mouse, a murine model of postnatal endolymphatic hydrops (ELH) undergo progressive deterioration reminiscent of human and other animal models of ELH with features suggesting apoptosis as an important mechanism.
  
  
  BACKGROUND
  Histologic analysis of the mutant's cochlea demonstrates ELH by postnatal Day (P) 21 and SGN loss by P90. The SGN loss seems to occur in a consistent topographic pattern beginning at the cochlear apex.
  
  
  METHODS
  SGN were counted at P60, P90, and P120. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative PCR, and immunohistochemical analyses of activated caspase-3, caspase-8, and caspase-9 were performed on cochlear sections obtained from mutants and controls. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay (TUNEL) was carried out on 2 mutants and 2 controls.
  
  
  RESULTS
  Corrected SGN counts in control mice were greater in the apical turn of the cochleae at P90 and P120, respectively (p < 0.01). Increased expression of activated caspase-3, caspase-8, and caspase-9 was seen in the mutant. At later time points, activated caspase expression gradually declined in the apical turns and increased in basal turns of the cochlea. Quantitative and semiquantitative PCR analysis confirmed increased expression of caspase-3, caspase-8, and caspase-9 at P21 and P40. TUNEL staining demonstrated apoptosis at P90 in the apical and basal turns of the mutant cochleae.
  
  
  CONCLUSIONS
  SGN degeneration in the Phex /Y mouse seems to mimic patterns observed in other animals with ELH. Apoptosis plays an important role in the degeneration of the SGN in the Phex male mouse.
authors: Department of Otolaryngology-Head and Neck Surgery, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA. maroun.semaan@UhHospitals.org
authors: Maroun T
authors: MT
authors: Semaan
authors: Qing Y
authors: QY
authors: Zheng
authors: Fengchan
authors: F
authors: Han
authors: Yuxi
authors: Y
authors: Zheng
authors: Heping
authors: H
authors: Yu
authors: John C
authors: JC
authors: Heaphy
authors: Cliff A
authors: CA
authors: Megerian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D018159:Endolymphatic Hydrops / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013136:Spiral Ganglion / Q000378:metabolism / Q000473:pathology*
chemical_list: D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9