Motile cilia genetics and cell biology: big results from little mice
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Cellular and Molecular Life Sciences
REVIEW
Motile cilia genetics and cell biology: big results from little mice Lance Lee1,2 · Lawrence E. Ostrowski3 Received: 29 April 2020 / Revised: 11 August 2020 / Accepted: 3 September 2020 © Springer Nature Switzerland AG 2020
Abstract Our understanding of motile cilia and their role in disease has increased tremendously over the last two decades, with critical information and insight coming from the analysis of mouse models. Motile cilia form on specific epithelial cell types and typically beat in a coordinated, whip-like manner to facilitate the flow and clearance of fluids along the cell surface. Defects in formation and function of motile cilia result in primary ciliary dyskinesia (PCD), a genetically heterogeneous disorder with a well-characterized phenotype but no effective treatment. A number of model systems, ranging from unicellular eukaryotes to mammals, have provided information about the genetics, biochemistry, and structure of motile cilia. However, with remarkable resources available for genetic manipulation and developmental, pathological, and physiological analysis of phenotype, the mouse has risen to the forefront of understanding mammalian motile cilia and modeling PCD. This is evidenced by a large number of relevant mouse lines and an extensive body of genetic and phenotypic data. More recently, application of innovative cell biological techniques to these models has enabled substantial advancement in elucidating the molecular and cellular mechanisms underlying the biogenesis and function of mammalian motile cilia. In this article, we will review genetic and cell biological studies of motile cilia in mouse models and their contributions to our understanding of motile cilia and PCD pathogenesis. Keywords Cilia · Motile cilia · Primary ciliary dyskinesia · PCD · Mouse · Mucociliary clearance
Introduction For more than a century, the mouse has been an indispensable tool for studying basic biological processes and modeling human disease [1–5]. Compared to other mammalian models, the mouse is an economic system with a small body size, a relatively short gestation period, and relatively large litters. In addition, the mouse is a particularly powerful genetic model with an impressive toolkit. With fully sequenced inbred strains and highly effective technologies for genetic manipulation, there is a remarkable capability to generate and study a wide array of genetic alleles * Lance Lee [email protected] 1
Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA
2
Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD, USA
3
Marsico Lung Institute/Cystic Fibrosis Center and Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
and modifiers of complex traits, including specific mutations identified in patients with human disease. Extensive repositories exist worldwide with a wide range of mouse models and tools available for biome
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