A new mouse model for retinal degeneration due to Fam161a deficiency
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Avigail Beryozkin
- Chen Matsevich
- Alexey Obolensky
- Corinne Kostic
- Yvan Arsenijevic
- Uwe Wolfrum
- Eyal Banin
- Dror Sharon
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000612982200173&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/s41598-021-81414-1
- Externe Identifier
- Clarivate Analytics Document Solution ID: PZ8HG
- PubMed Identifier: 33479377
- ISSN
- 2045-2322
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- SCIENTIFIC REPORTS
- Artikelnummer
- ARTN 2030
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Titel
- A new mouse model for retinal degeneration due to <i>Fam161a</i> deficiency
- Sub types
- Article
- Ausgabe der Zeitschrift
- 11
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p><jats:italic>FAM161A</jats:italic> mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, <jats:italic>Fam161a</jats:italic><jats:sup><jats:italic>tm1b/tm1b</jats:italic></jats:sup>, lacking the major exon #3 which was replaced by a construct that include LacZ under the expression of the <jats:italic>Fam161a</jats:italic> 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 <jats:italic>Fam161a</jats:italic> frameshift mutation affects retinal function and causes retinal degeneration. This model will be used for gene therapy treatment in the future.</jats:p>
- Autoren
- Avigail Beryozkin
- Chen Matsevich
- Alexey Obolensky
- Corinne Kostic
- Yvan Arsenijevic
- Uwe Wolfrum
- Eyal Banin
- Dror Sharon
- DOI
- 10.1038/s41598-021-81414-1
- eISSN
- 2045-2322
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Scientific Reports
- Sprache
- en
- Artikelnummer
- 2030
- Online publication date
- 2021
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/s41598-021-81414-1
- Datum der Datenerfassung
- 2022
- Titel
- A new mouse model for retinal degeneration due to Fam161a deficiency
- Ausgabe der Zeitschrift
- 11
Data source: Crossref
- 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.
- Addresses
- Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel.
- Autoren
- Avigail Beryozkin
- Chen Matsevich
- Alexey Obolensky
- Corinne Kostic
- Yvan Arsenijevic
- Uwe Wolfrum
- Eyal Banin
- Dror Sharon
- DOI
- 10.1038/s41598-021-81414-1
- eISSN
- 2045-2322
- Externe Identifier
- PubMed Identifier: 33479377
- PubMed Central ID: PMC7820261
- Funding acknowledgements
- Swiss National Science Foundation: Sinergia grant CRSII3_141814
- the Israeli Science Foundation: 1147/18
- Foundation Fighting Blindness: PPA-0717-0719-RAD
- Open access
- true
- ISSN
- 2045-2322
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Scientific reports
- Schlüsselwörter
- Retina
- Animals
- Mice, Knockout
- Humans
- Mice
- Retinitis Pigmentosa
- Retinal Degeneration
- Disease Models, Animal
- Calpain
- Eye Proteins
- Tomography, Optical Coherence
- Electroretinography
- Visual Acuity
- Frameshift Mutation
- Lac Operon
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2021
- Open access status
- Open Access
- Paginierung
- 2030
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2021
- Titel
- A new mouse model for retinal degeneration due to Fam161a deficiency.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 11
Files
https://www.nature.com/articles/s41598-021-81414-1.pdf https://europepmc.org/articles/PMC7820261?pdf=render
Data source: Europe PubMed Central
- Abstract
- FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161atm1b/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.
- Date of acceptance
- 2021
- Autoren
- Avigail Beryozkin
- Chen Matsevich
- Alexey Obolensky
- Corinne Kostic
- Yvan Arsenijevic
- Uwe Wolfrum
- Eyal Banin
- Dror Sharon
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33479377
- DOI
- 10.1038/s41598-021-81414-1
- eISSN
- 2045-2322
- Externe Identifier
- PubMed Central ID: PMC7820261
- Funding acknowledgements
- Swiss National Foundation: Sinergia grant CRSII3_141814
- Swiss National Foundation: Sinergia grant CRSII3_141814
- Swiss National Foundation: Sinergia grant CRSII3_141814
- Foundation Fighting Blindness: PPA-0717-0719-RAD
- the Israeli Science Foundation: 1147/18
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Sci Rep
- Schlüsselwörter
- Animals
- Calpain
- Disease Models, Animal
- Electroretinography
- Eye Proteins
- Frameshift Mutation
- Humans
- Lac Operon
- Mice
- Mice, Knockout
- Retina
- Retinal Degeneration
- Retinitis Pigmentosa
- Tomography, Optical Coherence
- Visual Acuity
- Sprache
- eng
- Country
- England
- Paginierung
- 2030
- PII
- 10.1038/s41598-021-81414-1
- Datum der Veröffentlichung
- 2021
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- A new mouse model for retinal degeneration due to Fam161a deficiency.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 11
Data source: PubMed
- Beziehungen:
- Property of