Fcgrt-KO Mouse

Fcgrt, also known as the gene encoding the neonatal Fc receptor (FcRn) alpha-chain, is of great significance. FcRn is a heterodimeric receptor, with its MHC-class-I-like protein encoded by Fcgrt. It binds endogenous IgG, protecting it from lysosomal degradation by transporting it back to the cell surface for re-entry into the circulation, thus extending the serum IgG lifespan. This process is crucial for maintaining appropriate IgG levels in the body and is involved in immune-related pathways [1].

In humans, variable number tandem repeat (VNTR) polymorphisms of Fcgrt can influence the expression levels of Fcgrt and IgG in serum. For example, in myasthenia gravis patients, VNTR3/2 polymorphisms in Fcgrt may affect the duration of infused IgG in the circulation and the effectiveness of intravenous immunoglobulin (IVIg) [1]. In rhesus macaques, 9 variants of Fcgrt VNTR polymorphism were identified, with the VNTR5 allele associated with lower IgG levels [2]. Also, Fcgrt has been found to be the uncoating receptor for major Enterovirus B, binding to virus particles in the "canyon" through its subunit, which is important for understanding enterovirus entry mechanisms [3]. DNA methylation in regulatory regions of Fcgrt in human liver and myocardium can impact FcRn expression, as methylation status in individual CpG sites correlates with Fcgrt mRNA expression [4]. In Indian water buffalo, nucleotide variants in Fcgrt are associated with colostral IgG concentration, which is vital for passive immunity transfer to newborn calves [5].

In conclusion, Fcgrt is essential for IgG recycling and transcytosis, influencing immune-related functions. Studies on Fcgrt, including those on its polymorphisms in different species and its role in various biological processes such as virus entry and tissue-specific expression regulation, contribute to our understanding of immune-related diseases, enterovirus-induced infections, and passive immunity transfer in neonates.

References:

1. Dalakas, Marinos C, Spaeth, Peter J. 2021. The importance of FcRn in neuro-immunotherapies: From IgG catabolism, FCGRT gene polymorphisms, IVIg dosing and efficiency to specific FcRn inhibitors. In Therapeutic advances in neurological disorders, 14, 1756286421997381. doi:10.1177/1756286421997381. https://pubmed.ncbi.nlm.nih.gov/33717213/

2. Pavlova, L E, Timina, M F, Agumava, A A, Panchenko, A V. 2024. Rhesus Macaques: VNTR Polymorphism of the FCGRT Gene. In Bulletin of experimental biology and medicine, 177, 379-382. doi:10.1007/s10517-024-06193-x. https://pubmed.ncbi.nlm.nih.gov/39134810/

3. Zhao, Xin, Zhang, Guigen, Liu, Sheng, Wei, Wensheng, Gao, George F. 2019. Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B. In Cell, 177, 1553-1565.e16. doi:10.1016/j.cell.2019.04.035. https://pubmed.ncbi.nlm.nih.gov/31104841/

4. Cejas, R B, Ferguson, D C, Quiñones-Lombraña, A, Bard, J E, Blanco, J G. 2019. Contribution of DNA methylation to the expression of FCGRT in human liver and myocardium. In Scientific reports, 9, 8674. doi:10.1038/s41598-019-45203-1. https://pubmed.ncbi.nlm.nih.gov/31209240/

5. Agrawal, Swati, Kumar, Subodh, Chaudhary, Rajni, Kumar, Amit, Sivamani, B. 2022. Detection of nucleotide variants in FCGRT (Fc fragment of IgG, receptor, transporter, alpha) gene and their influence on colostral IgG concentration in Indian water buffalo (Bubalus bubalis). In Molecular biology reports, 49, 3773-3781. doi:10.1007/s11033-022-07217-3. https://pubmed.ncbi.nlm.nih.gov/35152368/