The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation
| Autor: | M. Keith Wyatt, Phillip Cai, Katherine Peterson, Jianguo Fan, Joshua Lerner, Lijin Dong, Graeme Wistow |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Glycoside Hydrolases Blotting Western In situ hybridization Cataract Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience Chloride Channels CLIC5 Lens Crystalline medicine Animals RNA Messenger Northern blot Eye Proteins Fluorescent Antibody Technique Indirect Klotho In Situ Hybridization Mice Knockout Mice Inbred C3H biology Immunochemistry Wild type Membrane Proteins Cell Differentiation Epithelial Cells Blotting Northern Molecular biology Sensory Systems Lens Fiber Mice Inbred C57BL Ophthalmology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Lens (anatomy) biology.protein Normal lens Female Gene Deletion |
| Zdroj: | Experimental Eye Research. 169:111-121 |
| ISSN: | 0014-4835 |
| DOI: | 10.1016/j.exer.2018.02.001 |
| Popis: | KLPH/lctl belongs to the Klotho family of proteins. Expressed sequence tag analyses unexpectedly revealed that KLPH is highly expressed in the eye lens while northern blots showed that expression is much higher in the eye than in other tissues. In situ hybridization in mouse localized mRNA to the lens, particularly in the equatorial epithelium. Immunofluorescence detected KLPH in lens epithelial cells with highest levels in the germinative/differentiation zone. The gene for KLPH in mouse was deleted by homologous recombination. Littermate knockout (KO) and wild type (WT) mice were compared in a wide panel of pathology examinations and were all grossly normal, showing no systemic effects of the deletion. However, the lens, while superficially normal at young ages, had focusing defects and exhibited age-related cortical cataract by slit lamp examination. Whole-lens imaging showed that KO mice had disorganized lens sutures, forming a loose double-y or x instead of the tight y formation of WT. RNA-seq profiles for KO and WT littermates confirmed the absence of KLPH mRNA in KO lens and also showed complete absence of transcripts for Clic5, a protein associated with cilium/basal body related auditory defects in a mouse model. Immunofluorescence of lens epithelial flat mounts showed that Clic5 localized to cilia/centrosomes. Mice mutant for Clic5 (jitterbug) also had defective sutures. These results suggest that KLPH is required for lens-specific expression of Clic5 and that Clic5 has an important role in the machinery that controls lens fiber cell extension and organization. |
| Databáze: | OpenAIRE |
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