Gene expression differences in mouse placenta tissue bewteen wild-type and Zfp36l3 knockout mice. Mus musculus

The ZFP36L3 protein is a rodent-specific, placenta- and yolk sac-specific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. Zfp36l3 is paternally imprinted, with profound parent-of-origin effects on gene expression. RNASeq of KO placental mRNA revealed many significantly affected transcripts, some of which exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. The type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability. This receptor is critical for placental iron uptake from the maternal circulation, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life. Overall design: Examination of gene expression differences in mouse placenta tissue bewteen wild-type and Zfp36l3 knockout groups, each with 5 biological replicates

ZFP36L3蛋白是CCCH型串联锌指蛋白（CCCH tandem zinc finger proteins）家族中三联体脯氨酸富集蛋白（tristetraprolin, TTP）家族的成员，具有啮齿动物特异性，且仅表达于胎盘与卵黄囊中。
该家族蛋白可结合靶mRNA中的AU富集元件（AU-rich elements），并促进其脱腺苷酸化与降解。
ZFP36L3缺陷小鼠的新生存活率降低，但胎盘与存活子代未出现明显形态学异常。
Zfp36l3基因属于父本印记基因，对基因表达具有显著的亲本来源依赖性效应。
对敲除（knockout, KO）小鼠胎盘mRNA进行RNA测序（RNA-seq）分析，发现大量转录本的表达水平发生显著变化，其中部分转录本在来自敲除囊胚的分化型滋养层干细胞（trophoblast stem cells）中降解速率降低。
尽管1型转铁蛋白受体（type 1 transferrin receptor）mRNA的稳定性有所提升，但在敲除小鼠胎盘中其表达量却意外下调。
该受体对于胎盘从母体循环中摄取铁离子至关重要，其表达下调伴随敲除胎鼠体内铁储备降低，提示这种宫内铁缺乏可能对个体后期健康产生不良影响。
实验整体设计：对比野生型与Zfp36l3基因敲除组小鼠胎盘组织的基因表达差异，每组设置5个生物学重复样本。