Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype

Abstract Neuronal ceroid lipofuscinosis (NCL) type 1 (CLN1) is a neurodegenerative storage disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients suffer from brain atrophy, mental and motor retardation, seizures, and retinal dege...

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Autores principales:	Yevgeniya Atiskova, Susanne Bartsch, Tatyana Danyukova, Elke Becker, Christian Hagel, Stephan Storch, Udo Bartsch
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e94031a26164e6db766076287752ecd
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spelling	oai:doaj.org-article:5e94031a26164e6db766076287752ecd2021-12-02T15:08:20ZMice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype10.1038/s41598-019-50726-82045-2322https://doaj.org/article/5e94031a26164e6db766076287752ecd2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50726-8https://doaj.org/toc/2045-2322Abstract Neuronal ceroid lipofuscinosis (NCL) type 1 (CLN1) is a neurodegenerative storage disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients suffer from brain atrophy, mental and motor retardation, seizures, and retinal degeneration ultimately resulting in blindness. Here, we performed an in-depth analysis of the retinal phenotype of a PPT1-deficient mouse, an animal model of this condition. Reactive astrogliosis and microgliosis were evident in mutant retinas prior to the onset of retinal cell loss. Progressive accumulation of storage material, a pronounced dysregulation of various lysosomal proteins, and accumulation of sequestosome/p62-positive aggregates in the inner nuclear layer also preceded retinal degeneration. At advanced stages of the disease, the mutant retina was characterized by a significant loss of ganglion cells, rod and cone photoreceptor cells, and rod and cone bipolar cells. Results demonstrate that PPT1 dysfunction results in early-onset pathological alterations in the mutant retina, followed by a progressive degeneration of various retinal cell types at relatively late stages of the disease. Data will serve as a reference for future work aimed at developing therapeutic strategies for the treatment of retinal degeneration in CLN1 disease.Yevgeniya AtiskovaSusanne BartschTatyana DanyukovaElke BeckerChristian HagelStephan StorchUdo BartschNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-15 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yevgeniya Atiskova Susanne Bartsch Tatyana Danyukova Elke Becker Christian Hagel Stephan Storch Udo Bartsch Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
description	Abstract Neuronal ceroid lipofuscinosis (NCL) type 1 (CLN1) is a neurodegenerative storage disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients suffer from brain atrophy, mental and motor retardation, seizures, and retinal degeneration ultimately resulting in blindness. Here, we performed an in-depth analysis of the retinal phenotype of a PPT1-deficient mouse, an animal model of this condition. Reactive astrogliosis and microgliosis were evident in mutant retinas prior to the onset of retinal cell loss. Progressive accumulation of storage material, a pronounced dysregulation of various lysosomal proteins, and accumulation of sequestosome/p62-positive aggregates in the inner nuclear layer also preceded retinal degeneration. At advanced stages of the disease, the mutant retina was characterized by a significant loss of ganglion cells, rod and cone photoreceptor cells, and rod and cone bipolar cells. Results demonstrate that PPT1 dysfunction results in early-onset pathological alterations in the mutant retina, followed by a progressive degeneration of various retinal cell types at relatively late stages of the disease. Data will serve as a reference for future work aimed at developing therapeutic strategies for the treatment of retinal degeneration in CLN1 disease.
format	article
author	Yevgeniya Atiskova Susanne Bartsch Tatyana Danyukova Elke Becker Christian Hagel Stephan Storch Udo Bartsch
author_facet	Yevgeniya Atiskova Susanne Bartsch Tatyana Danyukova Elke Becker Christian Hagel Stephan Storch Udo Bartsch
author_sort	Yevgeniya Atiskova
title	Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
title_short	Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
title_full	Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
title_fullStr	Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
title_full_unstemmed	Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
title_sort	mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (ppt1) display a complex retinal phenotype
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/5e94031a26164e6db766076287752ecd
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Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype

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