Related Experiment Video
Updated: May 18, 2026
09:07
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Development of mice without Cip/Kip CDK inhibitors
Yuki Tateishi1, Akinobu Matsumoto, Tomoharu Kanie
1Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Fukuoka, Fukuoka 812-8582, Japan.
Biochemical and Biophysical Research Communications
|September 25, 2012
Summary
Mice lacking all three Cip/Kip cyclin-dependent kinase inhibitors (CKIs) die mid-gestation, showing developmental defects. p27 and p57 are crucial for development, while p21 has an auxiliary role.
Area of Science:
- Developmental Biology
- Cell Cycle Regulation
- Genetics
Background:
- Cyclin-dependent kinase inhibitors (CKIs) of the Cip/Kip family (p21, p27, p57) regulate cell cycle progression.
- These CKIs are believed to be essential for embryonic development.
- The functional redundancy among these CKIs is not fully understood.
Purpose of the Study:
- To investigate the functional redundancy of p21, p27, and p57 CKIs during mouse development.
- To determine the specific roles of each CKI and their combinations in embryonic development and cell cycle control.
Main Methods:
- Generation of knockout mice lacking combinations of Cip/Kip CKIs (single, double, and triple knockouts).
- Comparative analysis of embryonic development, morphology, and cell proliferation rates.
- Assessment of cell cycle profiles and CDK activity in mouse embryonic fibroblasts (MEFs).
Main Results:
- Triple knockout (TKO) embryos lacking all three CKIs (p21, p27, p57) exhibited developmental defects and died around embryonic day 13.5.
- TKO embryos showed morphological abnormalities and increased proliferation/apoptosis in the placenta and lens, similar to p27/p57 double knockouts (DKOs).
- MEFs lacking all three CKIs showed minimal differences in proliferation compared to controls, but exhibited increased CDK2 activity and decreased CDK4 activity/cyclin D1 abundance, more so than p27/p57 DKOs.
Conclusions:
- p27 and p57 are essential for mouse development post-midgestation.
- p21 plays a less critical, auxiliary role in normal embryonic development.
- Functional redundancy exists among Cip/Kip family members, with p27 and p57 being the primary drivers of developmental regulation.
Related Concept Videos
01:16In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
02:43Mouse Models of Cancer Study
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...