Premium
Partially redundant functions of Adamts1 and Adamts4 in the perinatal development of the renal medulla
Author(s) -
Boerboom Derek,
Lafond JeanFrançois,
Zheng Xiaofeng,
Lapointe Evelyne,
Mittaz Laureane,
Boyer Alexandre,
Pritchard Melanie A.,
DeMayo Francesco J.,
Mort John S.,
Drolet Richard,
Richards Joanne S.
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22662
Subject(s) - biology , andrology , renal medulla , medulla , phenotype , anatomy , kidney , medicine , endocrinology , gene , genetics
Adamts4 encodes a widely‐expressed proteinase thought to be involved in processes ranging from cartilage metabolism to ovarian follicle development. To study its physiological roles, Adamts4 ‐null mice were created by gene targeting. Unexpectedly, these were found to be phenotypically normal, suggesting that other gene(s) may compensate for its loss. Adamts4 −/− mice were, therefore, crossed with a strain lacking Adamts1 , whose pattern of expression and substrate specificity overlap that of Adamts4 . Most (>95%) Adamts1 −/− ; Adamts4 −/− mice died within 72 hr after birth with a marked thinning of the renal medulla. The renal defect was not observed in embryonic Adamts1 −/− ; Adamts4 −/− kidneys, but became apparent around birth. The few (<5%) Adamts1 −/− ; Adamts4 −/− animals to reach adulthood had the same renal phenotype seen in newborns. This study is thus the first to report Adamts4 expression and function in the mammalian kidney, and to demonstrate that Adamts1 and Adamts4 play redundant and essential roles in perinatal kidney development. Developmental Dynamics 240:1806–1814, 2011. © 2011 Wiley‐Liss, Inc.