In utero gene expression in the Slc39a8(neo/neo) knockdown mouse

Scientific Reports
Jing ChenDaniel W Nebert

Abstract

Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10-15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum, comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially-expressed genes revealed 29 unique genes from all tissues - having enriched GO categories associated with hematopoiesis and hypoxia and KEGG categories of complement, response to infection, and coagulation cascade - consistent with dysregulated hematopoietic stem cell fate. Based on transcription factor (TF) profiles in the JASPAR database, and searching for TF-binding sites enriched by Pscan, we identified numerous genes encoding zinc-finger and other TFs associated with hematopoietic stem cell functions. We conclude that, in this mouse model, deficient ZIP8-med...Continue Reading

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Citations

Sep 16, 2019·Human Genomics·Daniel W Nebert, Zijuan Liu
Oct 5, 2020·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Yanfang ZhaoXiaofeng Sheng
Aug 6, 2020·Scientific Reports·Robert G MealerJordan W Smoller

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Methods Mentioned

BETA
RNA-seq
glycosylation
PCR
chip

Software Mentioned

Pscan
JASPAR
R package
Canonical Pathway Analysis
R
ComplexHeatmap
Ingenuity Pathway Analysis ( IPA )
MouseMine

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