eCite Digital Repository

Nance-Horan syndrome protein, NHS, associates with epithelial cell junctions


Sharma, S and Ang, SL and Shaw, M and Mackey, DA and Gecz, J and McAvoy, JW and Craig, JE, Nance-Horan syndrome protein, NHS, associates with epithelial cell junctions, Human Molecular Genetics, 15, (12) pp. 1972-1983. ISSN 0964-6906 (2006) [Refereed Article]

DOI: doi:10.1093/hmg/ddl120


Nance-Horan syndrome, characterized by congenital cataracts, craniofacial, dental abnormalities and mental disturbances, is an X-linked disorder with significant phenotypic heterogeneity. Affected individuals have mutations in the NHS (Nance-Horan syndrome) gene typically resulting in premature truncation of the protein. This report underlines the complexity of the regulation of the NHS gene that transcribes several isoforms. We demonstrate the differential expression of the two NHS isoforms, NHS-A and NHS-1A, and differences in the subcellular localization of the proteins encoded by these isoforms. This may in part explain the pleiotropic features of the syndrome. We show that the endogenous and exogenous NHS-A isoform localizes to the cell membrane of mammalian cells in a cell-type-dependent manner and that it co-localizes with the tight junction (TJ) protein ZO-1 in the apical aspect of cell membrane in epithelial cells. We also show that the NHS-1A isoform is a cytoplasmic protein. In the developing mammalian lens, we found continuous expression of NHS that became restricted to the lens epithelium in pre- and postnatal lens. Consistent with the in vitro findings, the NHS-A isoform associates with the apical cell membrane in the lens epithelium. This study suggests that disturbances in intercellular contacts underlie cataractogenesis in the Nance-Horan syndrome. NHS is the first gene localized at TJs that has been implicated in congenital cataracts. © 2006 Oxford University Press.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:40068
Year Published:2006
Web of Science® Times Cited:36
Deposited By:Medicine
Deposited On:2006-08-01
Last Modified:2011-10-07

Repository Staff Only: item control page