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MRNA sequencing of brain and liver in multiple Alzheimer's Disease mouse models after treatment with either a Non-Targeting Control siRNA or an siRNA targeting mouse Apoe mRNA

ABSTRACT: mRNA sequencing of brain and liver in multiple Alzheimer's Disease mouse models after treatment with either a Non-Targeting Control siRNA or an siRNA targeting mouse Apoe mRNA

PROVIDER: PRJNA775977 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16611700.fastq.gz	Fastqsanger.gz
	SRR16611701.fastq.gz	Fastqsanger.gz
	SRR16611702.fastq.gz	Fastqsanger.gz
	SRR16611703.fastq.gz	Fastqsanger.gz
	SRR16611704.fastq.gz	Fastqsanger.gz

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mRNA sequencing of brain and liver in multiple Alzheimer's Disease mouse models after treatment with either a Non-Targeting Control siRNA or an siRNA targeting mouse Apoe mRNA

Project description:The most common genetic risk factor for late onset Alzheimer Disease (AD) is the APOE4 allele, with evidence for gain- and loss-of-function as a primary mechanism. ApoE knockout in mice abrogates AD phenotypes but causes severe atherosclerosis due to the role of liver ApoE in cholesterol homeostasis. Previous attempts to therapeutically block brain-specific ApoE in adult models of AD only modestly reduced ApoE expression and no significant impact on amyloid burden. Here, we optimized a divalent siRNA (di-siRNA) to selectively silence ApoE in brain (>2 months). By measuring transcriptomic changes upon knockdown of ApoE in the CNS in multiple mouse models of AD, we find that ApoE knockdown results in an upregulation of the innate immune response, likely through activation of microglia. Additionally, we find that the changes in the transcriptome were similar, but not identical, two weeks and two months post-treatment. We find that mild reduction of ApoE in the liver does not cause widespread transcriptomic changes, but near complete knockdown of ApoE in the liver results in the dysregulation of many lipid metabolism-related pathways.

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Expression data from Neuro2a cells treated with siRNA targeting to Cpeb1 mRNA.

Project description:Expression data from Neuro2a cells treated with siRNA targeting to Cpeb1 mRNA.

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Cynomolgus macaques treated with Divalent-siRNA (Di-siRNA) targeting Huntingtin gene

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Transcriptomic profile in in vitro produced mouse morula stage embryos treated with siRNA targeting Pwp1

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mRNA-Seq and 3'mRNA-Seq analyses of A2Lox mouse embryonic stem cells treated with control siRNA or siRNAs against Srrt or Ncbp1

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