PUBLICATION

FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing

Authors
Diaz-Horta, O., Subasioglu-Uzak, A., Grati, M., DeSmidt, A., Foster, J., Cao, L., Bademci, G., Tokgoz-Yilmaz, S., Duman, D., Cengiz, F.B., Abad, C., Mittal, R., Blanton, S., Liu, X.Z., Farooq, A., Walz, K., Lu, Z., Tekin, M.
ID
ZDB-PUB-140625-2
Date
2014
Source
Proceedings of the National Academy of Sciences of the United States of America   111(27): 9864-8 (Journal)
Registered Authors
Keywords
Mendelian disorder, congenital, deafness, sensorineural, whole-exome sequencing
MeSH Terms
  • Hearing Loss, Sensorineural/genetics
  • Stereocilia/physiology*
  • Subcellular Fractions/metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Mice
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Hearing/genetics
  • Hearing/physiology*
  • Turkey
  • RNA Splicing
  • Pedigree
  • Male
  • Animals
  • Zebrafish
  • Proteins/genetics
  • Proteins/metabolism
  • Proteins/physiology*
  • Female
(all 20)
PubMed
24958875 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
In a large consanguineous Turkish kindred with recessive nonsyndromic, prelingual, profound hearing loss, we identified in the gene FAM65B (MIM611410) a splice site mutation (c.102-1G>A) that perfectly cosegregates with the phenotype in the family. The mutation leads to exon skipping and deletion of 52-amino acid residues of a PX membrane localization domain. FAM65B is known to be involved in myotube formation and in regulation of cell adhesion, polarization, and migration. We show that wild-type Fam65b is expressed during embryonic and postnatal development stages in murine cochlea, and that the protein localizes to the plasma membranes of the stereocilia of inner and outer hair cells of the inner ear. The wild-type protein targets the plasma membrane, whereas the mutant protein accumulates in cytoplasmic inclusion bodies and does not reach the membrane. In zebrafish, knockdown of fam65b leads to significant reduction of numbers of saccular hair cells and neuromasts and to hearing loss. We conclude that FAM65B is a plasma membrane-associated protein of hair cell stereocilia that is essential for hearing.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
ripor2ABstandard conditionsProtruding-mouthISH
1 - 1 of 1
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Phenotype
Fish Conditions Stage Phenotype Figure
sqet4Et + MO1-ripor2standard conditionsProtruding-mouth
sqet4Et + MO1-ripor2standard conditionsProtruding-mouth
sqet4Et + MO1-ripor2standard conditionsProtruding-mouth
sqet4Et + MO2-ripor2standard conditionsProtruding-mouth
sqet4Et + MO2-ripor2standard conditionsProtruding-mouth
sqet4Et + MO2-ripor2standard conditionsProtruding-mouth
1 - 6 of 6
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sqet4EtTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    ripor2MO1-ripor2MRPHLNO
    ripor2MO2-ripor2MRPHLNO
    1 - 2 of 2
    Show
    Fish
    Fish
    AB
    sqet4Et
    sqet4Et + MO1-ripor2
    sqet4Et + MO2-ripor2
    1 - 4 of 4
    Show
    Antibodies
    No data available
    Orthology
    Gene Orthology
    ripor2
    1 - 1 of 1
    Show
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
    Show
    Mapping
    No data available
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    Citation
    Diaz-Horta, O., Subasioglu-Uzak, A., Grati, M., DeSmidt, A., Foster, J., Cao, L., Bademci, G., Tokgoz-Yilmaz, S., Duman, D., Cengiz, F.B., Abad, C., Mittal, R., Blanton, S., Liu, X.Z., Farooq, A., Walz, K., Lu, Z., Tekin, M. (2014) FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing. Proceedings of the National Academy of Sciences of the United States of America. 111(27):9864-8.