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Characterization of the Frmd7 knock-out mice generated by the EUCOMM/COMP repository as a model for Idiopathic Infantile Nystagmus (IIN)

Characterization of the Frmd7 knock-out mice generated by the EUCOMM/COMP repository as a model for Idiopathic Infantile Nystagmus (IIN)
Characterization of the Frmd7 knock-out mice generated by the EUCOMM/COMP repository as a model for Idiopathic Infantile Nystagmus (IIN)

In this study, we seek to exclude other pathophysiological mechanisms by which Frmd7 knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the Frmd7 .tm1a and Frmd7 .tm1b murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of Frmd7 gene in IIN using a novel murine model for the disease. We demonstrate that the Frmd7 .tm1b allele represents a more robust model of Frmd7 knock-out at the mRNA level. The expression of Frmd7 was investigated using both antibody staining and X-gal staining confirming previous reports that Frmd7 expression in the retina is restricted to starburst amacrine cells and demonstrating that X-gal staining recapitulates the expression pattern in this model. Thus, it offers a useful tool for further expression studies. We also show that gross retinal morphology and electrophysiology are unchanged in these Frmd7 mutant models when compared with wild-type mice. High-speed eye-tracking recordings of Frmd7 mutant mice confirm a specific horizontal optokinetic reflex defect. In summary, our study confirms the likely role for Frmd7 in the optokinetic reflex in mice mediated by starburst amacrine cells. We show that the Frmd7 .tm1b model provides a more robust knock-out than the Frmd7 .tm1a model at the mRNA level, although the functional consequence is unchanged. Finally, we establish a robust eye-tracking technique in mice that can be used in a variety of future studies using this model and others. Although our data highlight a deficit in the optiokinetic reflex as a result of the starburst amacrine cells in the retina, this does not rule out the involvement of other cells, in the brain or the retina where Frmd7 is expressed, in the pathophysiology of IIN.

FRMD7, Idiopathic Infantile Nystagmus, Nystagmus, Optokinetic nystagmus, Retina
2073-4425
1-20
Salman, Ahmed
c8e7fd8e-1821-4104-a148-d7d495d23ffe
Hutton, Samuel
6ef61486-e6fa-4114-9f19-a32e138853ee
Newall, Tutte
dcb33a14-8cbb-4ab1-ade1-ad59d8a47efc
Scott, Jennifer
bdc803de-3082-4727-a4ca-f5a1cf3fcfcc
Griffiths, Helen
a097fdaa-d3d6-49a9-9c69-0e6e5a5d518b
Lee, Helena
5d36fd1e-9334-4db5-b201-034d147133fb
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Self, James
0f6efc58-ae24-4667-b8d6-6fafa849e389
Salman, Ahmed
c8e7fd8e-1821-4104-a148-d7d495d23ffe
Hutton, Samuel
6ef61486-e6fa-4114-9f19-a32e138853ee
Newall, Tutte
dcb33a14-8cbb-4ab1-ade1-ad59d8a47efc
Scott, Jennifer
bdc803de-3082-4727-a4ca-f5a1cf3fcfcc
Griffiths, Helen
a097fdaa-d3d6-49a9-9c69-0e6e5a5d518b
Lee, Helena
5d36fd1e-9334-4db5-b201-034d147133fb
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Self, James
0f6efc58-ae24-4667-b8d6-6fafa849e389

Salman, Ahmed, Hutton, Samuel, Newall, Tutte, Scott, Jennifer, Griffiths, Helen, Lee, Helena, Gomez-Nicola, Diego, Lotery, Andrew and Self, James (2020) Characterization of the Frmd7 knock-out mice generated by the EUCOMM/COMP repository as a model for Idiopathic Infantile Nystagmus (IIN). Genes, 11 (10), 1-20, [1157]. (doi:10.3390/genes11101157).

Record type: Article

Abstract

In this study, we seek to exclude other pathophysiological mechanisms by which Frmd7 knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the Frmd7 .tm1a and Frmd7 .tm1b murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of Frmd7 gene in IIN using a novel murine model for the disease. We demonstrate that the Frmd7 .tm1b allele represents a more robust model of Frmd7 knock-out at the mRNA level. The expression of Frmd7 was investigated using both antibody staining and X-gal staining confirming previous reports that Frmd7 expression in the retina is restricted to starburst amacrine cells and demonstrating that X-gal staining recapitulates the expression pattern in this model. Thus, it offers a useful tool for further expression studies. We also show that gross retinal morphology and electrophysiology are unchanged in these Frmd7 mutant models when compared with wild-type mice. High-speed eye-tracking recordings of Frmd7 mutant mice confirm a specific horizontal optokinetic reflex defect. In summary, our study confirms the likely role for Frmd7 in the optokinetic reflex in mice mediated by starburst amacrine cells. We show that the Frmd7 .tm1b model provides a more robust knock-out than the Frmd7 .tm1a model at the mRNA level, although the functional consequence is unchanged. Finally, we establish a robust eye-tracking technique in mice that can be used in a variety of future studies using this model and others. Although our data highlight a deficit in the optiokinetic reflex as a result of the starburst amacrine cells in the retina, this does not rule out the involvement of other cells, in the brain or the retina where Frmd7 is expressed, in the pathophysiology of IIN.

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Accepted/In Press date: 24 September 2020
e-pub ahead of print date: 30 September 2020
Published date: October 2020
Keywords: FRMD7, Idiopathic Infantile Nystagmus, Nystagmus, Optokinetic nystagmus, Retina

Identifiers

Local EPrints ID: 444535
URI: http://eprints.soton.ac.uk/id/eprint/444535
ISSN: 2073-4425
PURE UUID: dfbdb085-0470-4c41-b960-d8653d82c170
ORCID for Helena Lee: ORCID iD orcid.org/0000-0002-2573-9536
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for James Self: ORCID iD orcid.org/0000-0002-1030-9963

Catalogue record

Date deposited: 23 Oct 2020 16:31
Last modified: 26 Nov 2021 03:04

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Contributors

Author: Ahmed Salman
Author: Samuel Hutton
Author: Tutte Newall
Author: Jennifer Scott
Author: Helen Griffiths
Author: Helena Lee ORCID iD
Author: Andrew Lotery ORCID iD
Author: James Self ORCID iD

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