Generating a Podocyte-Specific Neonatal F Receptor (FcRn) Knockout Mouse

Overview

Journal Methods Mol Biol

Specialty Molecular Biology

Date 2021 Feb 19

PMID 33606211

Authors

Judith Blaine

Affiliations

Soon will be listed here.

Abstract

Proteinuria is a widely used marker of renal disease and is strongly associated with renal and cardiovascular outcomes. The molecular mechanisms underlying filtration of serum proteins through the glomerular filtration barrier (GFB) remain to be determined. Since the GFB is a complex structure, studies of albumin or IgG trafficking in cultured cells in vitro may not fully recapitulate these processes in vivo. In other epithelial cells including renal proximal tubular cells, the neonatal Fc receptor (FcRn) is required to divert albumin and IgG from the degradative pathway which allows these proteins to be recycled or transcytosed. To examine the role of podocyte FcRn in albumin and IgG trafficking in vivo, we detail the creation of a podocyte-specific FcRn knockout mouse and describe methods for examining intraglomerular detection of albumin and IgG in these mice.

References

Hemmelgarn B, Manns B, Lloyd A, James M, Klarenbach S, Quinn R . Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010; 303(5):423-9. DOI: 10.1001/jama.2010.39. View

Kim J, Bronson C, Hayton W, Radmacher M, Roopenian D, Robinson J . Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces. Am J Physiol Gastrointest Liver Physiol. 2005; 290(2):G352-60. DOI: 10.1152/ajpgi.00286.2005. View

Castrop H, Schiessl I . Novel routes of albumin passage across the glomerular filtration barrier. Acta Physiol (Oxf). 2016; 219(3):544-553. DOI: 10.1111/apha.12760. View

Akilesh S, Huber T, Wu H, Wang G, Hartleben B, Kopp J . Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci U S A. 2008; 105(3):967-72. PMC: 2242706. DOI: 10.1073/pnas.0711515105. View

Kuo T, Baker K, Yoshida M, Qiao S, Aveson V, Lencer W . Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol. 2010; 30(6):777-89. PMC: 2970823. DOI: 10.1007/s10875-010-9468-4. View

Dickinson B . Unraveling the immunopathogenesis of glomerular disease. Clin Immunol. 2016; 169:89-97. DOI: 10.1016/j.clim.2016.06.011. View

Chaudhury C, Mehnaz S, Robinson J, Hayton W, Pearl D, Roopenian D . The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med. 2003; 197(3):315-22. PMC: 2193842. DOI: 10.1084/jem.20021829. View

Montoyo H, Vaccaro C, Hafner M, Ober R, Mueller W, Ward E . Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proc Natl Acad Sci U S A. 2009; 106(8):2788-93. PMC: 2650344. DOI: 10.1073/pnas.0810796106. View

Dylewski J, Dobrinskikh E, Lewis L, Tonsawan P, Miyazaki M, Jat P . Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo. PLoS One. 2019; 14(2):e0209732. PMC: 6392300. DOI: 10.1371/journal.pone.0209732. View

10.

Bakris G . Slowing nephropathy progression: focus on proteinuria reduction. Clin J Am Soc Nephrol. 2008; 3 Suppl 1:S3-10. PMC: 3152266. DOI: 10.2215/CJN.03250807. View

11.

Roopenian D, Christianson G, Sproule T, Brown A, Akilesh S, Jung N . The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol. 2003; 170(7):3528-33. DOI: 10.4049/jimmunol.170.7.3528. View

12.

Tenten V, Menzel S, Kunter U, Sicking E, van Roeyen C, Sanden S . Albumin is recycled from the primary urine by tubular transcytosis. J Am Soc Nephrol. 2013; 24(12):1966-80. PMC: 3839546. DOI: 10.1681/ASN.2013010018. View

13.

Scott R, Quaggin S . Review series: The cell biology of renal filtration. J Cell Biol. 2015; 209(2):199-210. PMC: 4411276. DOI: 10.1083/jcb.201410017. View

14.

Peti-Peterdi J . Independent two-photon measurements of albumin GSC give low values. Am J Physiol Renal Physiol. 2009; 296(6):F1255-7. PMC: 2692442. DOI: 10.1152/ajprenal.00144.2009. View

15.

Andersen J, Sandlie I . The versatile MHC class I-related FcRn protects IgG and albumin from degradation: implications for development of new diagnostics and therapeutics. Drug Metab Pharmacokinet. 2009; 24(4):318-32. DOI: 10.2133/dmpk.24.318. View

16.

Russo L, Sandoval R, McKee M, Osicka T, Collins A, Brown D . The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states. Kidney Int. 2007; 71(6):504-13. DOI: 10.1038/sj.ki.5002041. View