The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour.
Adaptor Proteins, Signal Transducing
Animals
Autism Spectrum Disorder
/ diagnostic imaging
Axons
Behavior, Animal
Brain
/ diagnostic imaging
DNA Copy Number Variations
Disease Models, Animal
Genetic Association Studies
Genetic Predisposition to Disease
/ genetics
Haploinsufficiency
Heterozygote
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins
/ genetics
Nervous System
/ metabolism
Nervous System Physiological Phenomena
/ genetics
Phenotype
Psychomotor Performance
Schizophrenia
/ diagnostic imaging
Sensory Gating
White Matter
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
21
11
2018
accepted:
20
06
2019
entrez:
3
8
2019
pubmed:
3
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric disorders characterized by defects in brain connectivity. Here, we show that CYFIP1 plays an important role in brain functional connectivity and callosal functions. We find that Cyfip1-heterozygous mice have reduced functional connectivity and defects in white matter architecture, similar to phenotypes found in patients with ASD, SCZ and other neuropsychiatric disorders. Cyfip1-deficient mice also present decreased myelination in the callosal axons, altered presynaptic function, and impaired bilateral connectivity. Finally, Cyfip1 deficiency leads to abnormalities in motor coordination, sensorimotor gating and sensory perception, which are also known neuropsychiatric disorder-related symptoms. These results show that Cyfip1 haploinsufficiency compromises brain connectivity and function, which might explain its genetic association to neuropsychiatric disorders.
Identifiants
pubmed: 31371726
doi: 10.1038/s41467-019-11203-y
pii: 10.1038/s41467-019-11203-y
pmc: PMC6672001
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Cyfip1 protein, mouse
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3454Commentaires et corrections
Type : CommentIn
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