Abnormal postpartum renal development and cystogenesis in the bcl
-2-/- mouse.
Sorenson, Christine M., Babu J. Padanilam, and Marc R. Hammerman.
George M. O'Brien Kidney and Urological Diseases Center, Renal
Division, Departments of Internal Medicine and Cell Biology and
Physiology, Washington University School of Medicine, St. Louis MO
63110
APStracts 3:0042F, 1996.
Mice deficient for B cell leukemia/lymphoma gene 2 (bcl-2-/- mice)
manifest congenital renal hypoplasia and develop multicystic kidney
disease and renal failure postnatally. To characterize postpartum
renal development, to identify the cellular origin of the cysts and
to provide insight into the role that bcl-2 deficiency plays in the
cystogenic process, we examined the morphology of kidneys from bcl-2
-/- mice and wild-type littermates (bcl-2+/+) from birth (P0) to post
-partum day 28 (P28), determined whether abnormalities of cellular
proliferation and apoptosis accompany cyst development and
characterized expression of the bcl-2-related protein, bax. Between
P0-P7, kidneys from bcl-2-/-, and bcl-2+/+ mice undergo a comparable
increase in weight, and have similar histological appearances.
However, during the next 2 weeks of life weight gain in kidneys from
bcl-2-/- mice is reduced compared to that in kidneys from bcl-2+/+
animals, and cysts develop in tubules with staining characteristics
of proximal tubule, distal tubule/medullary thick ascending limb of
Henle's loop and collecting duct. Unaffected glomeruli and proximal
tubules in kidneys of bcl-2-/- mice undergo compensatory growth.
Cystogenesis is accompanied by enhanced incorporation of 5-bromo-2'
-deoxyuridine in cells within cortex and medulla, and apoptosis of
cells within cysts and in the renal interstitium. Bax protein is
expressed in the distal tubule in kidneys of bcl-2+/+ and bcl-2-/-
mice, and in some, but not all cysts. We conclude that abnormal
regulation of DNA synthesis and apoptosis accompany cystogenesis in
bcl-2-/- mice during postpartum kidney development. Continued
expression of bax could enhance apoptotic cell death.
Received 6 September 1995; accepted in final form 23 February
1996.
APS Manuscript Number F298-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96