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

FASEB J. 2019 Jan;33(1):1440-1455. doi: 10.1096/fj.201801149R. Epub 2018 Aug 22.


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.

Keywords: ciliopathy; cystic kidney disease; obesity; retinal degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cilia / metabolism*
  • Ciliary Motility Disorders / genetics
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / genetics*
  • Encephalocele / genetics
  • Female
  • Genes, Lethal
  • Kidney Diseases, Cystic / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation*
  • Olfaction Disorders / genetics
  • Phenotype
  • Polycystic Kidney Diseases / genetics
  • Retinal Degeneration / genetics
  • Retinitis Pigmentosa / genetics
  • Tubulin / metabolism
  • Weight Gain / genetics


  • CC2D2A protein, mouse
  • Cytoskeletal Proteins
  • Tubulin

Supplementary concepts

  • Meckel syndrome type 1