期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：13
页码：5192-5197
DOI：10.1073/pnas.0811712106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Although p27 and p57 are structurally related cyclin-dependent kinase inhibitors (CKIs), and are thought to perform similar functions, p27 knockout (p27KO) and p57KO mice show distinct phenotypes. To elucidate the in vivo functions of these CKIs, we have now generated a knock-in mouse model (p57p27KI), in which the p57 gene has been replaced with the p27 gene. The p57p27KI mice are viable and appear healthy, with most of the developmental defects characteristic of p57KO mice having been corrected by p27 knock-in. Such developmental defects of p57KO mice were also ameliorated in mice deficient in both p57 and the transcription factor E2F1, suggesting that loss of p57 promotes E2F1-dependent apoptosis. The developmental defects apparent in a few tissues of p57KO mice were unaffected or only partially corrected by knock-in expression of p27. Thus, these observations indicate that p57 and p27 share many characteristics in vivo, but that p57 also performs specific functions not amenable to substitution with p27.
