PMID- 10655058
OWN - NLM
STAT- MEDLINE
DCOM- 20000228
LR  - 20081121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 24
IP  - 2
DP  - 2000 Feb
TI  - Targeted disruption of otog results in deafness and severe imbalance.
PG  - 139-43
AB  - Genes specifically expressed in the inner ear are candidates to underlie
      hereditary nonsyndromic deafness. The gene Otog has been isolated from a mouse
      subtractive cDNA cochlear library. It encodes otogelin, an N-glycosylated protein
      that is present in the acellular membranes covering the six sensory epithelial
      patches of the inner ear: in the cochlea (the auditory sensory organ), the
      tectorial membrane (TM) over the organ of Corti; and in the vestibule (the
      balance sensory organ), the otoconial membranes over the utricular and saccular
      maculae as well as the cupulae over the cristae ampullares of the three
      semi-circular canals. These membranes are involved in the mechanotransduction
      process. Their movement, which is induced by sound in the cochlea or acceleration
      in the vestibule, results in the deflection of the stereocilia bundle at the apex
      of the sensory hair cells, which in turn opens the mechanotransduction channels
      located at the tip of the stereo-cilia. We sought to elucidate the role of
      otogelin in the auditory and vestibular functions by generating mice with a
      targeted disruption of Otog. In Otog-/- mice, both the vestibular and the
      auditory functions were impaired. Histological analysis of these mutants
      demonstrated that in the vestibule, otogelin is required for the anchoring of the
      otoconial membranes and cupulae to the neuroepithelia. In the cochlea,
      ultrastructural analysis of the TM indicated that otogelin is involved in the
      organization of its fibrillar network. Otogelin is likely to have a role in the
      resistance of this membrane to sound stimulation. These results support OTOG as a
      possible candidate gene for a human nonsyndromic form of deafness.
FAU - Simmler, M C
AU  - Simmler MC
AD  - UMR 955 INRA de Genetique Moleculaire et Cellulaire, Ecole Nationale Veterinaire 
      d'Alfort, Maisons-Alfort Cedex, France.
FAU - Cohen-Salmon, M
AU  - Cohen-Salmon M
FAU - El-Amraoui, A
AU  - El-Amraoui A
FAU - Guillaud, L
AU  - Guillaud L
FAU - Benichou, J C
AU  - Benichou JC
FAU - Petit, C
AU  - Petit C
FAU - Panthier, J J
AU  - Panthier JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (OTOG protein, human)
RN  - 0 (Otog protein, mouse)
SB  - IM
CIN - Nat Genet. 2000 Feb;24(2):104. PMID: 10655048
MH  - Acoustic Stimulation
MH  - Animals
MH  - Chromosome Mapping
MH  - Cochlea/physiology/physiopathology
MH  - Deafness/*genetics/pathology/physiopathology
MH  - Ear, Inner/pathology/physiology/*physiopathology
MH  - Exons
MH  - Gene Library
MH  - Hearing Disorders/genetics/physiopathology
MH  - Humans
MH  - Membrane Glycoproteins/deficiency/*genetics/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Postural Balance/*physiology
MH  - Posture
MH  - Reflex/genetics
MH  - Stem Cells
MH  - Tectorial Membrane/pathology/*physiopathology/ultrastructure
MH  - Transfection
EDAT- 2000/02/02 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/02 09:00
PHST- 2000/02/02 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/02 09:00 [entrez]
AID - 10.1038/72793 [doi]
PST - ppublish
SO  - Nat Genet. 2000 Feb;24(2):139-43. doi: 10.1038/72793.