Deficiency of the neurodevelopmental disorder-associated gene Cyfip2 alters the retinal ganglion cell properties and visual acuity.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
21 02 2022
21 02 2022
Historique:
received:
26
06
2021
revised:
02
09
2021
accepted:
03
09
2021
pubmed:
12
9
2021
medline:
28
4
2022
entrez:
11
9
2021
Statut:
ppublish
Résumé
Intellectual disability (ID) is a neurodevelopmental disorder affecting approximately 0.5-3% of the population in the developed world. Individuals with ID exhibit deficits in intelligence, impaired adaptive behavior and often visual impairments. Cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2) is an interacting partner of the FMR protein, whose loss results in fragile X syndrome, the most common inherited cause of ID. Recently, CYFIP2 variants have been found in patients with early-onset epileptic encephalopathy, developmental delay and ID. Such individuals often exhibit visual impairments; however, the underlying mechanism is poorly understood. In the present study, we investigated the role of Cyfip2 in retinal and visual functions by generating and analyzing Cyfip2 conditional knockout (CKO) mice. While we found no major differences in the layer structures and cell compositions between the control and Cyfip2 CKO retinas, a subset of genes associated with the transporter and channel activities was differentially expressed in Cyfip2 CKO retinas than in the controls. Multi-electrode array recordings showed more sustained and stronger responses to positive flashes of the ON ganglion cells in the Cyfip2 CKO retina than in the controls, although electroretinogram analysis revealed that Cyfip2 deficiency unaffected the photoreceptor and ON bipolar cell functions. Furthermore, analysis of initial and late phase optokinetic responses demonstrated that Cyfip2 deficiency impaired the visual function at the organismal level. Together, our results shed light on the molecular mechanism underlying the visual impairments observed in individuals with CYFIP2 variants and, more generally, in patients with neurodevelopmental disorders, including ID.
Identifiants
pubmed: 34508581
pii: 6368510
doi: 10.1093/hmg/ddab268
pmc: PMC8863419
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
CYFIP2 protein, human
0
Cyfip2 protein, mouse
0
FMR1 protein, human
0
Fmr1 protein, mouse
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
535-547Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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