A new mouse model for retinal degeneration due to Fam161a deficiency

Abstract FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161a tm1b/tm1b , lacking the major exon #3 which was replaced by a construct that include LacZ under the expression of the Fam161a promoter. LacZ staining w...

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Autores principales:	Avigail Beryozkin, Chen Matsevich, Alexey Obolensky, Corinne Kostic, Yvan Arsenijevic, Uwe Wolfrum, Eyal Banin, Dror Sharon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad0c300bad8c4e92b277d31a4d21ab58
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spelling	oai:doaj.org-article:ad0c300bad8c4e92b277d31a4d21ab582021-12-02T15:23:47ZA new mouse model for retinal degeneration due to Fam161a deficiency10.1038/s41598-021-81414-12045-2322https://doaj.org/article/ad0c300bad8c4e92b277d31a4d21ab582021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81414-1https://doaj.org/toc/2045-2322Abstract FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161a tm1b/tm1b , 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.Avigail BeryozkinChen MatsevichAlexey ObolenskyCorinne KosticYvan ArsenijevicUwe WolfrumEyal BaninDror SharonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Avigail Beryozkin Chen Matsevich Alexey Obolensky Corinne Kostic Yvan Arsenijevic Uwe Wolfrum Eyal Banin Dror Sharon A new mouse model for retinal degeneration due to Fam161a deficiency
description	Abstract FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161a tm1b/tm1b , 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.
format	article
author	Avigail Beryozkin Chen Matsevich Alexey Obolensky Corinne Kostic Yvan Arsenijevic Uwe Wolfrum Eyal Banin Dror Sharon
author_facet	Avigail Beryozkin Chen Matsevich Alexey Obolensky Corinne Kostic Yvan Arsenijevic Uwe Wolfrum Eyal Banin Dror Sharon
author_sort	Avigail Beryozkin
title	A new mouse model for retinal degeneration due to Fam161a deficiency
title_short	A new mouse model for retinal degeneration due to Fam161a deficiency
title_full	A new mouse model for retinal degeneration due to Fam161a deficiency
title_fullStr	A new mouse model for retinal degeneration due to Fam161a deficiency
title_full_unstemmed	A new mouse model for retinal degeneration due to Fam161a deficiency
title_sort	new mouse model for retinal degeneration due to fam161a deficiency
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ad0c300bad8c4e92b277d31a4d21ab58
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A new mouse model for retinal degeneration due to Fam161a deficiency

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