Genomic Duplication and Overexpression of TJP2/ZO-2 Leads to Altered Expression of Apoptosis Genes in Progressive Nonsyndromic Hearing Loss DFNA51

Walsh, T., Pierce, S. B., Lenz, D. R., Brownstein, Z., Dagan-Rosenfeld, O., Shahin, H., Roeb, W., McCarthy, S. E., Nord, A. S., Gordon, C. R., Ben-Neriah, Z., Sebat, J., Kanaan, M., Lee, M. K., Frydman, M., King, M. C., Avraham, K. B. (July 2010) Genomic Duplication and Overexpression of TJP2/ZO-2 Leads to Altered Expression of Apoptosis Genes in Progressive Nonsyndromic Hearing Loss DFNA51. American Journal of Human Genetics, 87 (1). 101-109 .

URL: https://www.ncbi.nlm.nih.gov/pubmed/20602916
DOI: 10.1016/j.ajhg.2010.05.011

Abstract

Age-related hearing loss is due to death over time, primarily by apoptosis, of hair cells in the inner ear. Studies of mutant genes responsible for inherited progressive hearing loss have suggested possible mechanisms for hair cell death, but critical connections between these mutations and the causes of progressive hearing loss have been elusive. In an Israeli kindred, dominant, adult-onset, progressive nonsyndromic hearing loss DFNA51 is due to a tandem inverted genomic duplication of 270 kb that includes the entire wild-type gene encoding the tight junction protein TJP2 (ZO-2). In the mammalian inner ear, TJP2 is expressed mainly in tight junctions, and also in the cytoplasm and nuclei. TJP2 expression normally decreases with age from embryonic development to adulthood. In cells of affected family members, TJP2 transcript and protein are overexpressed, leading to decreased phosphorylation of GSK-3β and to altered expression of genes that regulate apoptosis. These results suggest that TJP2- and GSK-3β-mediated increased susceptibility to apoptosis of cells of the inner ear is the mechanism for adult-onset hearing loss in this kindred and may serve as one model for age-related hearing loss in the general population. © 2010 The American Society of Human Genetics.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organism description > animal behavior > auditory
organism description > animal behavior > auditory > hearing
CSHL Authors:
Communities: CSHL labs > McCombie lab
CSHL labs > Sebat lab
Depositing User: CSHL Librarian
Date: 9 July 2010
Date Deposited: 20 Oct 2011 13:49
Last Modified: 13 Mar 2018 15:21
PMCID: PMC2896780
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15579

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