p57(Kip2) regulates the proper development of labyrinthine and spongiotrophoblasts.

The cyclin-dependent kinase (cdk) inhibitor, p57 (Kip2) is a tumour suppressor candidate and a paternally-imprinted gene. In humans, the p57(Kip2) gene is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome. From analysis of p57(Kip2)-deficient mice, we demonstrate the relationship between trophoblastic abnormalities and p57(Kip2). Both p57(Kip2) null ((-/-)) embryos and heterozygous embryos with a maternally-derived mutated allele ((+*/-)) displayed placentomegaly, as well as dysplasia of labyrinthine and spongiotrophoblasts. The number of labyrinthine trophoblasts of homozygous embryos was twice that in wild-type embryos. When we measured kinase activities of cdk in total placenta lysates by the immuno complex kinase assay, there were no differences among the genotypes. These results show that p57(Kip2) may function in the proper development of labyrinthine and spongiotrophoblasts by pathways that are not involved with regulation of cdk activities. It is, therefore, suggested that p57(Kip2) protein might have an unknown role.