Impact of Genetic Background on Nephropathy in Diabetic Mice
Authors Susan B. Gurley, Sharon E. Clare, Kamie P. Snow, Timothy W. Meyer, and Thomas M.
Submitted By Thomas Coffman on 4/13/2005
Status Published
Journal American journal of physiology. Renal physiology
Year 2006
Date Published 1/1/2006
Volume : Pages 290 : F214 - F222
PubMed Reference 16118394
Abstract With the goal of identifying optimal platforms for developing better models of
diabetic nephropathy in mice, we compared renal effects of streptozotocin
(STZ)-induced diabetes among five common inbred mouse strains: C57BL/6, MRL/Mp,
BALB/c, DBA/2 and 129/SvEv. We also evaluated the renal consequences of chemical
and genetic (Akita mutation) diabetes on the same genetic background (C57BL/6).
There was a hierarchical response of blood glucose level to the STZ regimen
among the strains (DBA/2>C57BL/6>MRL/Mp>129/SvEv>BALB/c). In all five strains,
males demonstrated much more robust hyperglycemia with STZ than females.
Accordingly, our analysis of nephropathy focused on males from each strain.
STZ-induced diabetes was associated with modest levels of albuminuria in all of
the strains, but was greatest in the DBA/2 strain, which also had the most
marked hyperglycemia. Renal structural changes on light microscopy were limited
to the development of mesangial expansion, and while there were some apparent
differences among strains in susceptibility to renal pathological changes, there
was a significant positive correlation between blood glucose and the degree of
mesangial expansion suggesting that most of the variability in renal
pathological abnormalities was due to differences in hyperglycemia. While the
general character of renal involvement was similar between chemical and genetic
diabetes, Akita mice developed more marked hyperglycemia, elevated blood
pressures, and less variability in renal structural responses. Thus, among the
strains and models tested, the DBA/2 genetic background and the Akita model may
be the most useful platforms for model development.

Investigators with authorship
Thomas CoffmanDuke University Medical Center