title: Partially redundant functions of Adamts1 and Adamts4 in the perinatal development of the renal medulla.
abstract: 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.
authors.affiliation: Départment de Biomédecine Vétérinaire, Université de Montréal, St-Hyacinthe, Québec, Canada. derek.boerboom@umontreal.ca
authors.forename: Derek
authors.initials: D
authors.lastname: Boerboom
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lafond
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lapointe
authors.forename: Laureane
authors.initials: L
authors.lastname: Mittaz
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boyer
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Pritchard
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
authors.forename: John S
authors.initials: JS
authors.lastname: Mort
authors.forename: Richard
authors.initials: R
authors.lastname: Drolet
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Richards
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000818:Animals; D015153:Blotting, Western; D005260:Female; D007150:Immunohistochemistry; D007679:Kidney Medulla / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse