Zfp36l3-KO Mouse

Zfp36l3 is a member of the zinc finger protein 36 (ZFP36) family, which is involved in post-transcriptional regulation of messenger RNA (mRNA) metabolism [1]. It contains two tandemly repeated CCCH-type zinc-finger motifs and binds to adenine uridine-rich elements in the 3'-untranslated regions of specific mRNA, leading to target mRNA decay [1]. This gene is unique to rodents and is located on the X chromosome [2,3]. Zfp36l3 is particularly important for placental and extra-embryonic tissue function, suggesting its significance in female reproductive physiology and overall fecundity [2-4]. Genetic models, especially mouse models, are valuable for studying Zfp36l3's functions.

In Zfp36l3 knockout (KO) mice, neonatal survival rates decreased, indicating its importance for offspring survival [4]. RNA-Seq analysis of placental mRNA from KO mice showed many up-regulated transcripts, suggesting these are potential ZFP36L3 target mRNAs [4]. Among them, the type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite increased stability in KO stem cells [4]. Since this receptor is crucial for placental iron uptake, and its decrease was accompanied by decreased iron stores in the KO fetus, Zfp36l3 may be linked to placental iron metabolism [4].

In conclusion, Zfp36l3 is a rodent-specific gene playing essential roles in placental function, female fecundity, and potentially placental iron metabolism as revealed by KO mouse models. Understanding Zfp36l3 contributes to insights into rodent reproductive biology and potential implications for intrauterine deficiencies that may have long-term consequences.

References:

1. Makita, Sohei, Takatori, Hiroaki, Nakajima, Hiroshi. 2021. Post-Transcriptional Regulation of Immune Responses and Inflammatory Diseases by RNA-Binding ZFP36 Family Proteins. In Frontiers in immunology, 12, 711633. doi:10.3389/fimmu.2021.711633. https://pubmed.ncbi.nlm.nih.gov/34276705/

2. Gingerich, Timothy J, Stumpo, Deborah J, Lai, Wi S, Steppan, Scott J, Blackshear, Perry J. 2015. Emergence and evolution of Zfp36l3. In Molecular phylogenetics and evolution, 94, 518-530. doi:10.1016/j.ympev.2015.10.016. https://pubmed.ncbi.nlm.nih.gov/26493225/

3. Blackshear, Perry J, Phillips, Ruth S, Ghosh, Sanjukta, Richfield, Eric K, Lai, Wi S. 2005. Zfp36l3, a rodent X chromosome gene encoding a placenta-specific member of the Tristetraprolin family of CCCH tandem zinc finger proteins. In Biology of reproduction, 73, 297-307. doi:. https://pubmed.ncbi.nlm.nih.gov/15814898/

4. Stumpo, Deborah J, Trempus, Carol S, Tucker, Charles J, Bortner, Donna M, Blackshear, Perry J. 2016. Deficiency of the placenta- and yolk sac-specific tristetraprolin family member ZFP36L3 identifies likely mRNA targets and an unexpected link to placental iron metabolism. In Development (Cambridge, England), 143, 1424-33. doi:10.1242/dev.130369. https://pubmed.ncbi.nlm.nih.gov/26952984/