A new mouse model for retinal degeneration due to Fam161a deficiency.

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_56AD3917FBE0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A new mouse model for retinal degeneration due to Fam161a deficiency.
Journal
Scientific reports
Author(s)
Beryozkin A., Matsevich C., Obolensky A., Kostic C., Arsenijevic Y., Wolfrum U., Banin E., Sharon D.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
21/01/2021
Peer-reviewed
Oui
Volume
11
Number
1
Pages
2030
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161a <sup>tm1b/tm1b</sup> , lacking the major exon #3 which was replaced by a construct that include LacZ under the expression of the Fam161a promoter. LacZ staining was evident in ganglion cells, inner and outer nuclear layers and inner and outer-segments of photoreceptors in KO mice. No immunofluorescence staining of Fam161a was evident in the KO retina. Visual acuity and electroretinographic (ERG) responses showed a gradual decrease between the ages of 1 and 8 months. Optical coherence tomography (OCT) showed thinning of the whole retina. Hypoautofluorescence and hyperautofluorescence pigments was observed in retinas of older mice. Histological analysis revealed a progressive degeneration of photoreceptors along time and high-resolution transmission electron microscopy (TEM) analysis showed that photoreceptor outer segment disks were disorganized in a perpendicular orientation and outer segment base was wider and shorter than in WT mice. Molecular degenerative markers, such as microglia and CALPAIN-2, appear already in a 1-month old KO retina. These results indicate that a homozygous Fam161a frameshift mutation affects retinal function and causes retinal degeneration. This model will be used for gene therapy treatment in the future.
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2021 8:58
Last modification date
01/07/2021 5:37
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