Meckelin is necessary for photoreceptor intraciliary transport and outer segment morphogenesis.

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Animals, Cilia, Ciliary Motility Disorders, DNA, Disease Models, Animal, Encephalocele, Genotype, Immunohistochemistry, Membrane Proteins, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Morphogenesis, Mutation, Polycystic Kidney Diseases, Polymerase Chain Reaction, Protein Transport, Rod Cell Outer Segment

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Invest Ophthalmol Vis Sci 2012 Feb 23; 53(2):967-74.


PURPOSE: Cilia, complex structures found ubiquitously in most vertebrate cells, serve a variety of functions ranging from cell and fluid movement, cell signaling, tissue homeostasis, to sensory perception. Meckelin is a component of ciliary and cell membranes and is encoded by Tmem67 (Mks3). In this study, the retinal morphology and ciliary function in a mouse model for Meckel Syndrome Type 3 (MKS3) throughout the course of photoreceptor development was examined.

METHODS: To study the effects of a disruption in the Mks3 gene on the retina, the authors introduced a functional allele of Pde6b into B6C3Fe a/a-bpck/J mice and evaluated their retinas by ophthalmoscopic, histologic, and ultrastructural examination. In addition, immunofluorescence microscopy was used to assess protein trafficking through the connecting cilium and to examine the localization of ciliary and synaptic proteins in Tmem67(bpck) mice and controls.

RESULTS: Photoreceptors degenerate early and rapidly in bpck/bpck mutant mice. In addition, phototransduction proteins, such as rhodopsin, arrestin, and transducin, are mislocalized. Ultrastructural examination of photoreceptors reveal morphologically intact connecting cilia but dysmorphic and misoriented outer segment (OS) discs, at the earliest time point examined.

CONCLUSIONS: These findings underscore the important role for meckelin in intraciliary transport of phototransduction molecules and their effects on subsequent OS morphogenesis and maintenance.