Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice.
Adult
Animals
Carrier Proteins
/ genetics
Cilia
/ pathology
Ciliopathies
/ genetics
Disease Models, Animal
Female
Humans
Infertility, Male
/ genetics
Male
Membrane Transport Proteins
/ genetics
Mice
Mice, Knockout
Microtubules
/ metabolism
Middle Aged
Pedigree
Photophobia
/ genetics
Sperm Motility
/ genetics
Sperm Tail
/ pathology
Spermatogenesis
/ genetics
Syndrome
Transcription Factors
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
13
02
2019
accepted:
17
07
2019
revised:
29
08
2019
pubmed:
20
8
2019
medline:
8
1
2020
entrez:
20
8
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31425546
doi: 10.1371/journal.pgen.1008315
pii: PGENETICS-D-19-00246
pmc: PMC6715254
doi:
Substances chimiques
ARL2BP protein, human
0
Arl2bp protein, mouse
0
Carrier Proteins
0
Membrane Transport Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008315Subventions
Organisme : NEI NIH HHS
ID : R21 EY027707
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028035
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA148671
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA208875
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY025536
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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