ATP8B1 is essential for maintaining normal hearing
| Autor: | J.H.A.J. Curfs, Laura N. Bull, Roderick H. J. Houwen, Janneke M. Stapelbroek, Bert G. A. van Zanten, Theo A. Peters, Andy J. Beynon, Ronald P.J. Oude Elferink, Anneke Joosten, Bibian M. van Leeuwen, Denis H. A. van Beurden, Leo W. J. Klomp, Lieke M. van der Velden |
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| Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology |
| Rok vydání: | 2009 |
| Předmět: |
Genetics and epigenetic pathways of disease [NCMLS 6]
Hearing loss Stereocilia (inner ear) Hearing Loss Sensorineural Mutant Degeneration (medical) Biology Mice Cholestasis Hearing medicine otorhinolaryngologic diseases Animals Humans Phospholipid Transfer Proteins Organ of Corti Adenosine Triphosphatases Multidisciplinary Lipid asymmetry Anatomy Flippase Biological Sciences medicine.disease Mice Mutant Strains Cell biology medicine.anatomical_structure Evaluation of complex medical interventions [NCEBP 2] sense organs medicine.symptom Functional Neurogenomics [DCN 2] |
| Zdroj: | Proceedings of the National Academy of Sciences USA, 106, 24, pp. 9709-14 Proceedings of the National Academy of Sciences of the United States of America, 106(24), 9709-9714. National Academy of Sciences Proceedings of the National Academy of Sciences USA, 106, 9709-14 |
| ISSN: | 0027-8424 |
| Popis: | ATP8B1 deficiency is caused by autosomal recessive mutations in ATP8B1 , which encodes the putative phospatidylserine flippase ATP8B1 (formerly called FIC1). ATP8B1 deficiency is primarily characterized by cholestasis, but extrahepatic symptoms are also found. Because patients sometimes report reduced hearing capability, we investigated the role of ATP8B1 in auditory function. Here we show that ATP8B1/Atp8b1 deficiency, both in patients and in Atp8b1 G308V/G308V mutant mice, causes hearing loss, associated with progressive degeneration of cochlear hair cells. Atp8b1 is specifically localized in the stereocilia of these hair cells. This indicates that the mechanosensory function and integrity of the cochlear hair cells is critically dependent on ATP8B1 activity, possibly through maintaining lipid asymmetry in the cellular membranes of stereocilia. |
| Databáze: | OpenAIRE |
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