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Gene expression profile of wild type, PiZ and PiZ/Chop-/- mouse livers at two different ages

ABSTRACT: Gene expression profile of wild type, PiZ and PiZ/Chop-/- mouse livers at two different ages

PROVIDER: PRJNA594017 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10603421.fastq.gz	Fastqsanger.gz
	SRR10603422.fastq.gz	Fastqsanger.gz
	SRR10603423.fastq.gz	Fastqsanger.gz
	SRR10603424.fastq.gz	Fastqsanger.gz
	SRR10603425.fastq.gz	Fastqsanger.gz

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Gene expression profile of wild type, PiZ and PiZ/Chop-/- mouse livers at two different ages

Project description:To investigate the role of CHOP in the pathogenesis of liver disease due to Z alpha-1 antitrypsin in juvenile and older mice, we performed Quant-seq experiments at 6 and 36 weeks of age in wild type, PiZ and PiZ/Chop-/- mouse livers

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RNA-seq in livers of wild-type (WT) controls, PiZ and PIZ mice deleted for Chop (PiZ/Chop-/-)

Project description:Transgenic PiZ mice have been genetically engineered to express ATZ and have been a valuable experimental model for liver disease due to AAT polymerization. ATZ accumulates in these mice within the endoplamic reticulum (ER) of hepatocytes in a nearly identical manner to livers of affected patients. To investigate the role of the transcription factor CHOP in the pathogenesis of liver damage induced by ATZ, we performed RNA-seq in livers of 6-week-old wild type, PiZ and PiZ mice deleted for Chop. All groups were matched for the strain, age, and the gender.

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Gene expression analysis of PiZ mouse livers

Project description:Transgenic PiZ mice have been genetically engineered to express ATZ and have been a valuable experimental model for studing liver disease associated with AAT deficiency. ATZ accumulates in these mice within the ER of hepatocytes in a nearly identical manner to livers of affected patients. To investigate the pathogenesis of liver damage induced by ATZ, we performed gene expression analysis in livers of 6-week-old PiZ mice and strain-, age-, and gender-matched wild-type mouse controls. All samples were processed on Affymetrix Mouse 430A 2.0 arrays using GeneChip 3’-IVT Plus and Hybridization Wash and Stain kits by means of Affymetrix’s standard protocols. The analysis indicated that most genes upregulated in PiZ livers were associated with response to unfolded proteins, ER nuclear signaling pathway, and response to protein stimulus.

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Single cell analysis of naïve or AAV transduced NSG-PiZ mouse livers

Project description:To determine whether different hepatotropic AAV capsids can mediate transduction of human hepatocytes in liver-humanized chimeric mice we performed an experiment in NSG-PiZ mice. NSG-PiZ mice were simultaneously administered barcoded AAV vectors with capsids derived from AAV8, AAV9, AAVrh10, AAVDJ/8 and AAV.LK03 at a total dose of 1E12 vg per mouse. At 14 days post delivery naïve and AAV treated mice were sacrificed and livers perfused to generate single cell suspensions for scRNA-seq. We transplanted mice with human hepatocytes from 2 donors (4 mice per donor) and half of the mice from each donor were adminsitered AAV.

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Liver miRNA profile of PiZ mice

Project description:Transgenic PiZ mice have been genetically engineered to express ATZ and have been a valuable experimental model for liver disease due to AAT polymerization. ATZ accumulates in these mice within the ER of hepatocytes in a nearly identical manner to livers of affected patients. MiRNAs play a key role in a wide range of biological processes and regulate gene expression mainly at the translational level. To search for miRNA with altered expression in AAT liver disease, we analyzed by miRNA next generation sequencing (NGS) the livers of 6-week-old PiZ mice and strain-, age-, and gender-matched wild-type mouse controls. This analysis revealed 70 miRNAs with differential expressions.

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