Skip to main content
SpringerLink
Log in

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

  • Protocol
  • First Online:
Mouse Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2224))

  • 1132 Accesses

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bakris GL (2008) Slowing nephropathy progression: focus on proteinuria reduction. Clin J Am Soc Nephrol 3:S3–S10

    Article  CAS  Google Scholar 

  2. Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M (2010) Relation between kidney function, proteinuria, and adverse outcomes. JAMA 303:423–429

    Article  CAS  Google Scholar 

  3. Scott RP, Quaggin SE (2015) Review series: the cell biology of renal filtration. J Cell Biol 209:199–210

    Article  CAS  Google Scholar 

  4. Peti-Peterdi J (2009) Independent two-photon measurements of albumin GSC give low values. Am J Physiol Ren Physiol 296:F1255–F1257

    Article  CAS  Google Scholar 

  5. Russo LM, Sandoval RM, McKee M, Osicka TM, Collins AB, Brown D, Molitoris BA, Comper WD (2007) The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states. Kidney Int 71:504–513

    Article  CAS  Google Scholar 

  6. Castrop H, Schiessl IM (2016) Novel routes of albumin passage across the glomerular filtration barrier. Acta Physiol (Oxford, England) 219(3):544–553

    Google Scholar 

  7. Kuo T, Baker K, Yoshida M, Qiao S-W, Aveson V, Lencer W, Blumberg R (2010) Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol 30:777–789

    Article  CAS  Google Scholar 

  8. Dickinson BL (2016) Unraveling the immunopathogenesis of glomerular disease. Clin Immunol 169:89–97

    Article  CAS  Google Scholar 

  9. Andersen JT, Sandlie I (2009) The Versatile MHC class I-related FcRn protects IgG and albumin from degradation: implications for development of new diagnostics and therapeutics. Drug Metab Pharmacokinet 24:318–332

    Article  CAS  Google Scholar 

  10. Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL (2003) The major histocompatibility complex–related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 197:315–322

    Article  CAS  Google Scholar 

  11. Kim J, Bronson CL, Hayton WL, Radmacher MD, Roopenian DC, Robinson JM, Anderson CL (2006) Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces. Am J Physiol Gastrointest Liver Physiol 290:G352–G360

    Article  CAS  Google Scholar 

  12. Tenten V, Menzel S, Kunter U, Sicking E-M, van Roeyen CRC, Sanden SK, Kaldenbach M, Boor P, Fuss A, Uhlig S, Lanzmich R, Willemsen B, Dijkman H, Grepl M, Wild K, Kriz W, Smeets B, Floege J, Moeller MJ (2013) Albumin is recycled from the primary urine by tubular transcytosis. J Am Soc Nephrol 24(12):1966–1980

    Article  CAS  Google Scholar 

  13. Akilesh S, Huber TB, Wu H, Wang G, Br H, Kopp JB, Miner JH, Roopenian DC, Unanue ER, Shaw AS (2008) Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci USA 105:967–972

    Article  CAS  Google Scholar 

  14. Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N, Petkova S, Avanessian L, Choi EY, Shaffer DJ, Eden PA, Anderson CL (2003) The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 170:3528–3533

    Article  CAS  Google Scholar 

  15. Montoyo HP, Vaccaro C, Hafner M, Ober RJ, Mueller W, Ward ES (2009) Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proc Natl Acad Sci 106:2788–2793

    Article  CAS  Google Scholar 

  16. Dylewski J, Dobrinskikh E, Lewis L, Tonsawan P, Miyazaki M, Jat PS, Blaine J (2019) Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo. PLoS One 14:e0209732

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded by a Norman Coplon Satellite Healthcare grant and NIH R01DK104264 to JB.

Author information

Authors and Affiliations

  1. Division of Renal Diseases and Hypertension, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

    Judith Blaine

Authors
  1. Judith Blaine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Judith Blaine .

Editor information

Editors and Affiliations

  1. Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA

    Shree Ram Singh

  2. Department of Surgery, University of California, AntiCancer, Inc., San Diego, CA, USA

    Robert M. Hoffman

  3. Department of Biology, University of Dayton, Dayton, OH, USA

    Amit Singh

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Blaine, J. (2021). Generating a Podocyte-Specific Neonatal F Receptor (FcRn) Knockout Mouse. In: Singh, S.R., Hoffman, R.M., Singh, A. (eds) Mouse Genetics . Methods in Molecular Biology, vol 2224. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1008-4_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1008-4_9

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1007-7

  • Online ISBN: 978-1-0716-1008-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation