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Transcriptional characterization of the Eif2b5[R191H] loss-of-function mouse model

ABSTRACT: Transcriptional characterization of the Eif2b5[R191H] loss-of-function mouse model

PROVIDER: PRJNA1002365 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25525600.fastq.gz	Fastqsanger.gz
	SRR25525601.fastq.gz	Fastqsanger.gz
	SRR25525602.fastq.gz	Fastqsanger.gz
	SRR25525603.fastq.gz	Fastqsanger.gz
	SRR25525604.fastq.gz	Fastqsanger.gz

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Transcriptional characterization of the Eif2b5[R191H] loss-of-function mouse model

Project description:The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. We have characterized an eIF2B loss of function (LOF) mouse model, carrying the homozygous Eif2b5[R191H] mutation that is homologous to the Vanishing White Matter Disease (VWMD)-causing human R195H variant. Characterization of previously reported transcript markers in animals 3-4 weeks of age confirmed ISR activation in the brain, but not in heterozygous or wild-type littermates.The robust elevation of ISR markers was further confirmed in bulk brain RNA sequencing analysis of a separate cohort of homozygous mutants and wild-type littermates. Known ATF4 targets feature prominently among the most strongly up-regulated genes in the eIF2B mutant compared to WT littermates.

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