Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.

<h4>Background</h4>Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this...

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Autores principales:	Francis Béby, Michael Housset, Nicolas Fossat, Coralie Le Greneur, Frédéric Flamant, Pierre Godement, Thomas Lamonerie
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7ca3b07f86740ce812c39905222f9e3
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spelling	oai:doaj.org-article:c7ca3b07f86740ce812c39905222f9e32021-12-02T20:19:53ZOtx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.1932-620310.1371/journal.pone.0011673https://doaj.org/article/c7ca3b07f86740ce812c39905222f9e32010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20657788/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells.<h4>Methodology/principal findings</h4>Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease.<h4>Conclusions</h4>Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE.Francis BébyMichael HoussetNicolas FossatCoralie Le GreneurFrédéric FlamantPierre GodementThomas LamoneriePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11673 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francis Béby Michael Housset Nicolas Fossat Coralie Le Greneur Frédéric Flamant Pierre Godement Thomas Lamonerie Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
description	<h4>Background</h4>Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells.<h4>Methodology/principal findings</h4>Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease.<h4>Conclusions</h4>Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE.
format	article
author	Francis Béby Michael Housset Nicolas Fossat Coralie Le Greneur Frédéric Flamant Pierre Godement Thomas Lamonerie
author_facet	Francis Béby Michael Housset Nicolas Fossat Coralie Le Greneur Frédéric Flamant Pierre Godement Thomas Lamonerie
author_sort	Francis Béby
title	Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
title_short	Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
title_full	Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
title_fullStr	Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
title_full_unstemmed	Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
title_sort	otx2 gene deletion in adult mouse retina induces rapid rpe dystrophy and slow photoreceptor degeneration.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/c7ca3b07f86740ce812c39905222f9e3
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Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.

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