Although p27 and p57 are structurally related cyclin-dependent kinase inhibitors (CKIs), and are thought to perform similar functions, p27 knockout (p27 KO) and p57 KO mice show distinct phenotypes. Toelucidate theinvivo functionsofthese CKIs, wehave now generated a knock-in mouse model (p57 p27KI), in which the p57 gene has been replaced with the p27 gene. The p57 27KI mice are viable and appear healthy, with mostof the developmental defects characteristic ofp57 KOmice having been correctedbyp27 knock-in. Such developmental defects of p57 KO 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 p57 KO 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.
|Number of pages
|Proceedings of the National Academy of Sciences of the United States of America
|Published - 2009 Mar 31
- Cell cycle