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Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone.

Citation
Lewis, W. R., et al. “Mks6 Mutations Reveal Tissue- And Cell Type-Specific Roles For The Cilia Transition Zone.”. Faseb Journal : Official Publication Of The Federation Of American Societies For Experimental Biology, pp. 1440-1455.
Center Indiana University University of Alabama at Birmingham
Multicenter
Multicenter
Author Wesley R Lewis, Katie L Bales, Dustin Z Revell, Mandy J Croyle, Staci E Engle, Cheng Jack Song, Erik B Malarkey, Cedric R Uytingco, Dan Shan, Patrick J Antonellis, Tim R Nagy, Robert A Kesterson, Michal M Mrug, Jeffrey R Martens, Nicolas F Berbari, Alecia K Gross, Bradley K Yoder
Keywords ciliopathy, cystic kidney disease, obesity, retinal degeneration
Abstract

The transition zone (TZ) is a domain at the base of the cilium that is involved in maintaining ciliary compartment-specific sensory and signaling activity by regulating cilia protein composition. Mutations in TZ proteins result in cilia dysfunction, often causing pleiotropic effects observed in a group of human diseases classified as ciliopathies. The purpose of this study is to describe the importance of the TZ component Meckel-Grüber syndrome 6 ( Mks6) in several organ systems and tissues regarding ciliogenesis and cilia maintenance using congenital and conditional mutant mouse models. Similar to MKS, congenital loss of Mks6 is embryonic lethal, displaying cilia loss and altered cytoskeletal microtubule modifications but only in specific cell types. Conditional Mks6 mutants have a variable cystic kidney phenotype along with severe retinal degeneration with mislocalization of phototransduction cascade proteins. However, other phenotypes, such as anosmia and obesity, which are typically associated with cilia and TZ dysfunction, were not evident. These data indicate that despite Mks6 being a core TZ component, it has tissue- or cell type-specific functions important for cilia formation and cilia sensory and signaling activities. Lewis, W. R., Bales, K. L., Revell, D. Z., Croyle, M. J., Engle, S. E., Song, C. J., Malarkey, E. B., Uytingco, C. R., Shan, D., Antonellis, P. J., Nagy, T. R., Kesterson, R. A., Mrug, M. M., Martens, J. R., Berbari, N. F., Gross, A. K., Yoder, B. K. Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone.

Year of Publication
2019
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
33
Issue
1
Number of Pages
1440-1455
Date Published
12/2019
ISSN Number
1530-6860
DOI
10.1096/fj.201801149R
Alternate Journal
FASEB J.
PMID
30133325
PMCID
PMC6355093
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