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A mutation in transmembrane protein 135 impairs lipid metabolism in mouse eyecups.

ABSTRACT: Aging is a significant factor in the development of age-related diseases but how aging disrupts cellular homeostasis to cause age-related retinal disease is unknown. Here, we further our studies on transmembrane protein 135 (Tmem135), a gene involved in retinal aging, by examining the transcriptomic profiles of wild-type, heterozygous and homozygous Tmem135 mutant posterior eyecup samples through RNA sequencing (RNA-Seq). We found significant gene expression changes in both heterozygous and homozygous Tmem135 mutant mouse eyecups that correlate with visual function deficits. Further analysis revealed that expression of many genes involved in lipid metabolism are changed due to the Tmem135 mutation. Consistent with these changes, we found increased lipid accumulation in mutant Tmem135 eyecup samples. Since mutant Tmem135 mice have similar ocular pathologies as human age-related macular degeneration (AMD) eyes, we compared our homozygous Tmem135 mutant eyecup RNA-Seq dataset with transcriptomic datasets of human AMD donor eyes. We found similar changes in genes involved in lipid metabolism between the homozygous Tmem135 mutant eyecups and AMD donor eyes. Our study suggests that the Tmem135 mutation affects lipid metabolism as similarly observed in human AMD eyes, thus Tmem135 mutant mice can serve as a good model for the role of dysregulated lipid metabolism in AMD.

SUBMITTER: Landowski M

PROVIDER: S-EPMC8760256 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A Mutation in Transmembrane Protein 135 Impairs Lipid Metabolism in Mouse Eyecups

Project description:Aging is a significant factor in the development of age-related diseases but the molecular underpinnings of how aging disrupts cellular homeostasis to cause retinal disease is unknown. Here, we further our studies on Transmembrane protein 135 (Tmem135), a gene involved in retinal aging, by examining the transcriptomic profiles of wildtype, heterozygous and homozygous Tmem135 mutant posterior eyecup samples through RNA sequencing (RNA-Seq). We found significant gene expression changes in both heterozygous and homozygous Tmem135 mutant mouse eyecups that correlates with visual function deficits. Further analysis revealed many genes involved in lipid metabolism are changed due to the Tmem135 mutation. We confirm these changes by finding increased lipid accumulation in mutant Tmem135 eyecup samples. Since mutant Tmem135 mice have similar ocular pathologies as human age-related macular degeneration (AMD) eyes, we compared our homozygous Tmem135 mutant eyecup RNA-Seq dataset with datasets of human AMD donor eyes. We find similar changes in genes involved in lipid metabolism between the homozygous Tmem135 mutant eyecups and AMD donor eyes. Our study suggests that the Tmem135 mutation affects lipid metabolism as similarly observed in human AMD eyes, thus Tmem135 mutant mice can serve as a good model for the role of dysregulated lipid metabolism in AMD.

2021-09-22 | GSE184160 | GEO

A Mutation in Transmembrane Protein 135 Impairs Lipid Metabolism in Mouse Eyecups

Project description:A Mutation in Transmembrane Protein 135 Impairs Lipid Metabolism in Mouse Eyecups

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