Resistance to Glomerulosclerosis in B6 Mice Disappears after Menopause
The American Journal of Pathology. 2003-04-01; 162(4): 1339-1348
DOI: 10.1016/s0002-9440(10)63929-6
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1. Am J Pathol. 2003 Apr;162(4):1339-48. doi: 10.1016/S0002-9440(10)63929-6.
Resistance to glomerulosclerosis in B6 mice disappears after menopause.
Zheng F(1), Plati AR, Potier M, Schulman Y, Berho M, Banerjee A, Leclercq B,
Zisman A, Striker LJ, Striker GE.
Author information:
(1)Vascular Biology Institute, Department of Medicine, University of Miami
School of Medicine, Miami, Florida 33136, USA.
The frequency of chronic renal failure increases with age, especially in women
after menopause. Glomerulosclerosis is a common cause of chronic renal failure
in aging. We reported that pre-menopausal female C57BL6 (B6) mice are resistant
to glomerulosclerosis, irrespective of the type of injury. However, we now show
that B6 mice develop progressive glomerulosclerosis after menopause. Glomerular
lesions, first recognized in 18-month-old mice, consisted of hypertrophy,
vascular pole sclerosis, and mesangial cell proliferation. Diffuse but moderate
mesangial sclerosis and more marked hypertrophy were present at 22 months. At 28
to 30 months the glomerulosclerosis was diffuse and increased levels of type I
and type IV collagen and transforming growth factor-beta 1 mRNA were present.
Urine albumin excretion was significantly increased in 30-month-old mice.
Mesangial cells isolated from 28-month-old mice retained their sclerotic
phenotype in vitro. Comparison of the effects of uninephrectomy (Nx) in
20-month-old and 2.5-month-old mice revealed a 1.7-fold increase in urine
albumin excretion, accelerated glomerulosclerosis, and renal function
insufficiency in 20-month-old Nx mice, but not in 2.5-month-old Nx mice.
Glycemic levels, glucose, insulin tolerance, and blood pressure were normal at
all ages. Thus, B6 mice model the increased frequency of chronic renal failure
in postmenopausal women and provide a model for studying the mechanism(s) of
glomerulosclerosis in aging women.
DOI: 10.1016/S0002-9440(10)63929-6
PMCID: PMC1851217
PMID: 12651625 [Indexed for MEDLINE]