APOL1-G0 or APOL1-G2 transgenic models develop preeclampsia but not kidney disease

Leslie A. Bruggeman, Zhenzhen Wu, Liping Luo, Sethu M. Madhavan, Martha Konieczkowski, Paul E. Drawz, David B. Thomas, Laura Barisoni, John R. Sedor, John F. O'Toole

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


APOL1 risk variants are associatedwith kidney disease in blacks, but themechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes fromTg-G0 and Tg-G2mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.

Original languageEnglish (US)
Pages (from-to)3600-3610
Number of pages11
JournalJournal of the American Society of Nephrology
Issue number12
StatePublished - Dec 2016

Bibliographical note

Publisher Copyright:
Copyright © 2016 by the American Society of Nephrology.


Dive into the research topics of 'APOL1-G0 or APOL1-G2 transgenic models develop preeclampsia but not kidney disease'. Together they form a unique fingerprint.

Cite this