Skip to main content

Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.

Publication ,  Journal Article
Bruggeman, LA; Dikman, S; Meng, C; Quaggin, SE; Coffman, TM; Klotman, PE
Published in: J Clin Invest
July 1, 1997

HIV-associated nephropathy (HIVAN) is a progressive glomerular and tubular disease that is increasingly common in AIDS patients and one of the leading causes of end stage renal disease in African Americans. A major unresolved issue in the pathogenesis of HIVAN is whether the kidney disease is due to renal cell infection or a "bystander" phenomenon mediated by systemically dysregulated cytokines. To address this issue, we have used two different experimental approaches and an HIV-1 transgenic mouse line that develops a progressive renal disease histologically similar to HIVAN in humans. In the murine model, kidney tissue expresses the transgene and in heterozygous adults, renal disease develops shortly thereafter. We demonstrate by terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labeling assay that similar to the disease in humans, apoptosis of renal tubular epithelial cells is a component of the molecular pathogenesis. To determine whether apoptosis is due to transgene expression or environmental factors, we treated fetal kidney explants (normal and transgenic) with UV light to induce transgene expression. Apoptosis occurred in transgenic but not normal littermates after stimulation of transgene expression. To confirm a direct effect of HIV expression on the production of HIVAN, we transplanted kidneys between normal and transgenic mice. HIVAN developed in transgenic kidneys transplanted into nontransgenic littermates. Normal kidneys remained disease free when transplanted into transgenic littermates. Thus, the renal disease in the murine model is intrinsic to the kidney. Using two different experimental approaches, we demonstrate a direct effect of transgene expression on the development of HIVAN in the mouse. These studies suggest that in humans, a direct effect of HIV-1 expression is likely the essential cause of HIVAN, rather than an indirect effect of cytokine dysregulation.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

July 1, 1997

Volume

100

Issue

1

Start / End Page

84 / 92

Location

United States

Related Subject Headings

  • United States
  • Ultraviolet Rays
  • Mice, Transgenic
  • Mice
  • Kidney Tubules
  • Kidney Transplantation
  • Kidney
  • Immunology
  • Humans
  • HIV-1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bruggeman, L. A., Dikman, S., Meng, C., Quaggin, S. E., Coffman, T. M., & Klotman, P. E. (1997). Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression. J Clin Invest, 100(1), 84–92. https://doi.org/10.1172/JCI119525
Bruggeman, L. A., S. Dikman, C. Meng, S. E. Quaggin, T. M. Coffman, and P. E. Klotman. “Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.J Clin Invest 100, no. 1 (July 1, 1997): 84–92. https://doi.org/10.1172/JCI119525.
Bruggeman LA, Dikman S, Meng C, Quaggin SE, Coffman TM, Klotman PE. Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression. J Clin Invest. 1997 Jul 1;100(1):84–92.
Bruggeman, L. A., et al. “Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.J Clin Invest, vol. 100, no. 1, July 1997, pp. 84–92. Pubmed, doi:10.1172/JCI119525.
Bruggeman LA, Dikman S, Meng C, Quaggin SE, Coffman TM, Klotman PE. Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression. J Clin Invest. 1997 Jul 1;100(1):84–92.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

July 1, 1997

Volume

100

Issue

1

Start / End Page

84 / 92

Location

United States

Related Subject Headings

  • United States
  • Ultraviolet Rays
  • Mice, Transgenic
  • Mice
  • Kidney Tubules
  • Kidney Transplantation
  • Kidney
  • Immunology
  • Humans
  • HIV-1