학술논문
Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice.
Document Type
Article
Author
Moye, Abigail R.; Bedoni, Nicola; Cunningham, Jessica G.; Sanzhaeva, Urikhan; Tucker, Eric S.; Mathers, Peter; Peter, Virginie G.; Quinodoz, Mathieu; Paris, Liliana P.; Coutinho-Santos, Luísa; Camacho, Pedro; Purcell, Madeleine G.; Winkelmann, Abbie C.; Foster, James A.; Pugacheva, Elena N.; Rivolta, Carlo; Ramamurthy, Visvanathan
Source
Subject
*MICROTUBULES
*MALE infertility
*CEREBRAL ventricles
*MEN
*CYTOLOGY
*CELL anatomy
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Language
ISSN
1553-7390
Abstract
Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP, encoding the ADP-Ribosylation Factor Like 2 Binding Protein. In this study, we have identified multiple ciliopathy phenotypes associated with mutations in ARL2BP in human patients and in a mouse knockout model. Our research demonstrates that spermiogenesis is impaired, resulting in abnormally shaped heads, shortened and mis-assembled sperm tails, as well as in loss of axonemal doublets. Additional phenotypes in the mouse included enlarged ventricles of the brain and situs inversus. Mouse embryonic fibroblasts derived from knockout animals revealed delayed depolymerization of primary cilia. Our results suggest that ARL2BP is required for the structural maintenance of cilia as well as of the sperm flagellum, and that its deficiency leads to syndromic ciliopathy. [ABSTRACT FROM AUTHOR]