title: Prolyl 3-hydroxylase-1 null mice exhibit hearing impairment and abnormal morphology of the middle ear bone joints.
abstract: Prolyl 3-hydroxylase1 (P3H1) is a collagen modifying enzyme which hydroxylates certain prolines in the Xaa position of conventional GlyXaaYaa triple helical sequence. Recent investigations have revealed that mutations in the LEPRE1 (gene encoding for P3H1) cause severe osteogenesis imperfecta (OI) in humans. Similarly LEPRE1 knockout mice display an OI-like phenotype. Significant hearing loss is a common problem for people with osteogenesis imperfecta. Here we report that hearing of the P3H1 null mice is substantially affected. Auditory brainstem responses (ABRs) of the P3H1 null mice show an average increase of 20-30 dB in auditory thresholds. Three dimensional reconstructions of the mutant middle ear bones by Micro-scale X-ray computed tomography (Micro-CT) demonstrate abnormal morphology of the incudostapedial and incudomalleal joints. We establish the LEPRE1 knockout mouse as a valuable model system to investigate the mechanism of hearing loss in recessive OI.
authors.affiliation: Research Department, Shriners Hospitals for Children, Portland, OR 97239, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Pokidysheva
authors.forename: Sara
authors.initials: S
authors.lastname: Tufa
authors.forename: Chris
authors.initials: C
authors.lastname: Bresee
authors.forename: John V
authors.initials: JV
authors.lastname: Brigande
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Bächinger
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D004429:Ear Ossicles / Q000002:abnormalities*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005808:Genes, Recessive / Q000235:genetics; D034381:Hearing Loss / Q000201:enzymology / Q000235:genetics*; D007596:Joints / Q000002:abnormalities*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010013:Osteogenesis Imperfecta / Q000201:enzymology / Q000235:genetics*; D011393:Procollagen-Proline Dioxygenase / Q000172:deficiency*; D011509:Proteoglycans / Q000235:genetics*; D055114:X-Ray Microtomography
chemical_list: C485658:Lepre1 protein, mouse; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase