Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice.
p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display symptoms similar to preeclampsia. p57-/+ (heterozygotes for p57Kip2 ) female mice that were mated with p57-/+ males showed hypertension, proteinuria, thrombocytopenia, decreased anti-thrombin III activity, and increased endothelin levels during late pregnancy. In their kidneys, endotheliosis of glomeruli were recognized along with fibrinoid or hyalinoid deposits. These characteristics were also observed in pregnant p57-/+ females that were mated with wild type males, but not in pregnant wild type females mated with p57-/+ males or wild type males. The pregnant p57-/+ mice had conceptuses both with and without p57Kip2 expression. The conceptuses without p57Kip2 expression showed trophoblastic hyperplasia, which mimics the hallmark proliferation of intermediate trophoblasts in clinical preeclampsia. It is suggested that the preeclampsia-like symptoms of the pregnant p57-/+ mice might have been induced by the conceptus(es) without p57Kip2 expression. In addition, pregnant p57-/+ mice might serve as a new animal model for preeclampsia characterized by trophoblastic hyperplasia.
Kanayama
Naohiro
N
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine 3600, Handa-cho, Hamamatsu, Shizuoka 431-3192, Japan. kanayama@ham-med.ac.jp
Takahashi
Katsuhiko
K
Matsuura
Toshiki
T
Sugimura
Motoi
M
Kobayashi
Takao
T
Moniwa
Nobuhiko
N
Tomita
Motowo
M
Nakayama
Keiko
K
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D050761:Cyclin-Dependent Kinase Inhibitor p57; D005260:Female; D018392:Genomic Imprinting; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011507:Proteinuria / Q000503:physiopathology; D013921:Thrombocytopenia / Q000503:physiopathology; D014327:Trophoblasts / Q000502:physiology*
C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins