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Jianguo Fan, Joshua Lerner, Philip Cai, Lijing Dong, Graeme Wistow; The Klotho- related KLPH/Lctl is highly expressed in lens epithelium and is required for expression of Clic5 and normal suture formation in mouse lens. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1215.
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© ARVO (1962-2015); The Authors (2016-present)
KLPH (Lctl) belongs to the Klotho gene family that is implicated in aging. KLPH is highly and preferentially expressed in the lens. Our goal is to examine its localization and provide insight on how it functions in the lens.
KLPH expression in mouse lens was localized by in situ hybridization, immuno-staining and western blotting. The murine KLPH gene locus was deleted by homologous recombination. Effects of KLPH deletion on the lens were examined using through-the-lens and live lens imaging with light and confocal fluorescence microscopy. Effects of KLPH deletion on gene expression in lens were examined by RNA-seq.
KLPH is a 70 kDa protein that forms a disulfide-linked dimer. KLPH mRNA and protein expression were localized to the lens epithelium and superficial fiber cells. KLPH protein was also found in both lens epithelia and lens fibers. Deletion of KLPH led to altered suture formation in the young mouse lenses, similar to models of defective planar cell polarity (PCP) in lens, and defective focusing in the aged mouse lenses. RNA-seq and western blotting showed that KLPH deletion led to complete loss of expression of Clic5, a putative chloride channel that is associated with cilia. Immunolabeling of Clic5 in wild type lens epithelium whole mount showed that Clic5 is localized to the fiber cell cilia.
These data suggest that KLPH has a lens-preferred role as an important regulator of normal lens fiber organization, and that it acts through tissue-specific regulation of Clic5.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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