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Updated: Jan 24, 2026
High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia
Published on: January 19, 2022
A null allele of Dnaaf2 displays embryonic lethality and mimics human ciliary dyskinesia
Agnes Cheong1, Rinat Degani1, Kimberly D Tremblay1
1Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Abstract:
The dynein axonemal assembly factor (Dnaaf) protein family is involved in preassembly and stability of dynein arms before they are transported into the cilia. In humans, mutations in DNAAF genes lead to several diseases related to cilia defects such as primary ciliary dyskinesia (PCD; OMIM: 612518). Patients with PCD experience malfunctions in cilia motility, which can result in inflammation and infection of the respiratory tract among other defects. Previous studies have identified that a mutation in DNAAF2 results in PCD and that 40% of these patients also experience laterality defects. In an outbred genetic background, Dnaaf2 homozygotes die after birth and have left/right defects among other phenotypes. Here we characterize a novel null allele of Dnaaf2 obtained from the International Mouse Phenotyping Consortium. Our data indicate that on a defined C57bl/6NJ genetic background, homozygous Dnaaf2 mouse embryos fail to progress beyond organogenesis stages with many abnormalities including left-right patterning defects. These findings support studies indicating that hypomorphic mutations of human DNAAF2 can result in ciliary dyskinesia and identify Dnaaf2 as an essential component of cilia function in vivo.
Insights
Dynein axonemal assembly factor 2 (Dnaaf2) is crucial for cilia function and embryonic development. Loss of Dnaaf2 causes severe developmental abnormalities and left-right patterning defects in mice, highlighting its role in human ciliopathies like primary ciliary dyskinesia.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Dynein axonemal assembly factors (Dnaaf) are essential for ciliary function.
- Mutations in human DNAAF genes cause primary ciliary dyskinesia (PCD), a disease affecting cilia motility.
- DNAAF2 mutations are linked to PCD and laterality defects in humans.
Purpose of the Study:
- To characterize a novel null allele of Dnaaf2 in mice.
- To investigate the in vivo role of Dnaaf2 during embryonic development.
- To understand the consequences of Dnaaf2 deficiency on cilia formation and function.
Main Methods:
- Generation and characterization of a novel Dnaaf2 null allele.
- Phenotypic analysis of Dnaaf2 homozygous mutant mice on a C57bl/6NJ background.
- Embryonic development and organogenesis assessment.
Main Results:
- Homozygous Dnaaf2 mutant mouse embryos exhibit developmental arrest at organogenesis.
- Significant abnormalities, including left-right patterning defects, were observed in mutant embryos.
- Dnaaf2 is essential for normal embryonic development and cilia function in vivo.
Conclusions:
- Dnaaf2 is indispensable for embryonic development and proper left-right patterning.
- The study validates Dnaaf2 as a critical component of cilia assembly and function.
- Findings support the link between Dnaaf2 deficiency and human ciliopathies like PCD.
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