Prg2-KO Mouse

Prg2, also known as plasticity-related gene 2 or phospholipid phosphatase-related protein 3 (PLPPR3), has multiple functions. In neurons, it is involved in axon morphogenesis by inhibiting the phosphatase PTEN, thus stabilizing membrane PI(3,4,5)P3 and promoting axon filopodia and branch formation [2,4]. It is also associated with the immune process related to eosinophils [3].

In placenta previa and percreta, PRG2 protein levels are upregulated in fetal membranes and the placental disk, and its mislocalization is observed in fetal membranes, suggesting it may be a marker for these conditions and related to increased trophoblast invasiveness [1]. In neuropsychiatric systemic lupus erythematosus (NPSLE), PRG2 protein is overexpressed in patient serum and correlates with the SLE disease activity index subset scores of psychosis [3]. In bullous pemphigoid, PRG2 is among the immune-related proteins whose activities are inhibited by dupilumab treatment [5]. A GWAS in Sardinians found that a signal within the PRG2 gene has a large effect size on eosinophil scatter, and a Sardinian-specific PRG2 mutation may explain changes in eosinophil morphology [6]. In imatinib-resistant CML cells, 5-Azacytidine re-expresses PRG2, inactivates STAT3, and increases sensitivity to imatinib, suggesting PRG2 may be a tumor suppressor gene [7].

In summary, Prg2 plays crucial roles in neuronal development, immune-related processes, and is associated with various diseases such as placenta-related disorders, NPSLE, bullous pemphigoid, and CML. Studies on Prg2, including those using gene-related models, help understand its functions in normal biological processes and disease mechanisms, potentially providing new insights for disease diagnosis, treatment, and prevention.

References:

1. Zhang, Elisa T, Hannibal, Roberta L, Badillo Rivera, Keyla M, Lyell, Deirdre J, Baker, Julie C. . PRG2 and AQPEP are misexpressed in fetal membranes in placenta previa and percreta†. In Biology of reproduction, 105, 244-257. doi:10.1093/biolre/ioab068. https://pubmed.ncbi.nlm.nih.gov/33982062/

2. Brosig, Annika, Fuchs, Joachim, Ipek, Fatih, Leondaritis, George, Eickholt, Britta J. . The Axonal Membrane Protein PRG2 Inhibits PTEN and Directs Growth to Branches. In Cell reports, 29, 2028-2040.e8. doi:10.1016/j.celrep.2019.10.039. https://pubmed.ncbi.nlm.nih.gov/31722215/

3. Qiao, Xiaoyue, Lu, Li, Zhou, Kangxing, Liang, Jun, Dou, Huan. 2022. The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus. In Clinical immunology (Orlando, Fla.), 239, 109042. doi:10.1016/j.clim.2022.109042. https://pubmed.ncbi.nlm.nih.gov/35568106/

4. Fuchs, Joachim, Eickholt, Britta J, Leondaritis, George. 2020. Harnessing PTEN's Growth Potential in Neuronal Development and Disease. In Neuroscience insights, 15, 2633105520959056. doi:10.1177/2633105520959056. https://pubmed.ncbi.nlm.nih.gov/32974612/

5. Yan, Tianmeng, Xie, Yinghan, Liu, Yuhua, Zuo, Ya-Gang, Zhang, Zhenying. 2023. Dupilumab effectively and rapidly treats bullous pemphigoid by inhibiting the activities of multiple cell types. In Frontiers in immunology, 14, 1194088. doi:10.3389/fimmu.2023.1194088. https://pubmed.ncbi.nlm.nih.gov/37575240/

6. Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Cucca, Francesco, Zoledziewska, Magdalena. . GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology. In Human molecular genetics, 32, 790-797. doi:10.1093/hmg/ddac238. https://pubmed.ncbi.nlm.nih.gov/36136759/

7. Al-Jamal, Hamid Ali Nagi, Johan, Muhammad Farid, Mat Jusoh, Siti Asmaa, Ismail, Imilia, Wan Taib, Wan Rohani. 2018. Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells. In Asian Pacific journal of cancer prevention : APJCP, 19, 1585-1590. doi:. https://pubmed.ncbi.nlm.nih.gov/29936783/