2,8-dihydroxyadenine nephrolithiasis induces developmental stage-specific alterations in gene expression in mouse kidney.
OBJECTIVE
To identify factors that may be crucial for the initiation and progression of stone-induced injury in the developing mouse kidney by a prospective observational study using microarray analysis. Kidney stone diseases are common in premature infants, but the underlying molecular and cellular mechanisms are not fully defined.


METHODS
Mice with adenine phosphoribosyltransferase deficiency develop 2,8-dihydroxyadenine (DHA) nephrolithiasis. The gene expression changes between Aprt(-/-) and Aprt(+/+) kidneys from newborn and adult mice were compared using Affymetrix gene chips. Targets of interest were further analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry.


RESULTS
We identified a set of genes that were differentially expressed in the developing kidney in response to DHA-induced injury. In 1-week-old Aprt(-/-) mice, the expression of Sprr2f and Clu was highly augmented and that of Egf was significantly decreased. We also observed that maturation-related gene expression changes were delayed in developing Aprt(-/-) kidneys, and immature Aprt(-/-) kidneys contained large numbers of intercalated cells that were blocked from terminal differentiation.


CONCLUSIONS
This study presents a comprehensive picture of the transcriptional changes induced by DHA stone injury in the developing mouse kidney. Our findings help explain growth impairment in kidneys subject to injury during the early stages of development.
Chen
Jianmin
J
Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
Chen
Yanping
Y
Capizzi
Stephanie
S
Yang
Min
M
Deng
Li
L
Bledsoe
Sharon B
SB
Evan
Andrew P
AP
Tischfield
Jay A
JA
Sahota
Amrik
A
D000225:Adenine / Q000031:analogs & derivatives*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000254:growth & development*; D051379:Mice; D046228:Microarray Analysis; D053040:Nephrolithiasis / Q000235:genetics*
C002993:2,8-dihydroxyadenine; D000225:Adenine