Functional loss of Ccdc151 leads to hydrocephalus in a mouse model of primary ciliary dyskinesia

Disease Models & Mechanisms
Francesco ChianiGlauco P Tocchini-Valentini

Abstract

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder affecting normal structure and function of motile cilia, phenotypically manifested as chronic respiratory infections, laterality defects and infertility. Autosomal recessive mutations in genes encoding for different components of the ciliary axoneme have been associated with PCD in humans and in model organisms. The CCDC151 gene encodes for a coiled-coil axonemal protein that ensures correct attachment of outer dynein arm (ODA) complexes to microtubules. A correct arrangement of dynein arm complexes is required to provide the proper mechanical force necessary for cilia beat. Loss-of-function mutations in CCDC151 in humans leads to PCD disease with respiratory distress and defective left-right body asymmetry. In mice with the Ccdc151Snbl loss-of-function mutation (Snowball mutant), left-right body asymmetry with heart defects have been observed. Here, we demonstrate that loss of Ccdc151 gene function via targeted gene deletion in mice leads to perinatal lethality and congenital hydrocephalus. Microcomputed tomography (microCT) X-ray imaging of Ccdc151-β-galactosidase reporter expression in whole-mount brain and histological analysis show that Ccdc151 is exp...Continue Reading

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Citations

Aug 18, 2020·Neurology. Genetics·Evie Alexandra RobsonChristopher O'Callaghan
Sep 12, 2020·Cellular and Molecular Life Sciences : CMLS·Lance Lee, Lawrence E Ostrowski
Mar 7, 2020·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Oct 20, 2020·Human Molecular Genetics·Xinbao DingJohn C Schimenti
Mar 28, 2021·Pharmacology & Therapeutics·Max Duong PhuMelanie Philipp
Jul 9, 2021·Fluids and Barriers of the CNS·Vijay KumarJaebong Kim

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Methods Mentioned

BETA
X-ray
Knockout
reverse transcription PCR
gene knockout
dissection
transgenic
PCR

Software Mentioned

Allen Mouse Common Coordinate Framework
Brain Explorer2
PICADAR
CTvox analyzer
NRecon Skyscan
ImageJ
Bruker MicroCT - Analyser
CTvox
Bruker

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