Mutations in Hydin impair ciliary motility in mice.
Chlamydomonas reinhardtii hydin is a central pair protein required for flagellar motility, and mice with Hydin defects develop lethal hydrocephalus. To determine if defects in Hydin cause hydrocephalus through a mechanism involving cilia, we compared the morphology, ultrastructure, and activity of cilia in wild-type and hydin mutant mice strains. The length and density of cilia in the brains of mutant animals is normal. The ciliary axoneme is normal with respect to the 9 + 2 microtubules, dynein arms, and radial spokes but one of the two central microtubules lacks a specific projection. The hydin mutant cilia are unable to bend normally, ciliary beat frequency is reduced, and the cilia tend to stall. As a result, these cilia are incapable of generating fluid flow. Similar defects are observed for cilia in trachea. We conclude that hydrocephalus in hydin mutants is caused by a central pair defect impairing ciliary motility and fluid transport in the brain.
Lechtreck
Karl-Ferdinand
KF
Department of Cell, University of Massachusetts Medical School, Worcester, MA 01655, USA. Karl.Lechtreck@umassmed.edu
Delmotte
Philippe
P
Robinson
Michael L
ML
Sanderson
Michael J
MJ
Witman
George B
GB
D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D002552:Cerebral Ventricles / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004805:Ependyma / Q000002:abnormalities / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics; D020545:Respiratory Mucosa / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D014132:Trachea / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure
C481382:Hydin protein, mouse; D008840:Microfilament Proteins