Cyclin F disruption compromises placental development and affects normal cell cycle execution.
Human cyclin F was originally isolated as a cDNA capable of suppressing the temperature sensitivity of a Saccharomyces cerevisiae cdc4-1 mutant. Its tightly regulated expression and high conservation in the evolutionary progression from amphibians to mammals suggest that it coordinates the timing of a critical cell cycle event. The fact that it contains an F box and can form an SCF (Skp1-Cul1/Cdc53-F-box) complex in vivo further suggests that it may also function in proteolysis. To investigate the role of cyclin F in vivo, we generated mice deficient for cyclin F and conditionally deficient mice as well as mouse embryonic fibroblasts (MEFs) conditionally deficient for cyclin F. Heterozygous animals are normal and fertile, but CycF(-/-) animals, with a myriad of developmental anomalies due in large part to failures in yolk sac and chorioallantoic placentation, die around embryonic day 10.5. Tissue-specific deletion of cyclin F revealed that it was not required for the development and function of a number of different embryonic and adult tissues. In contrast, MEFs lacking cyclin F, while viable, do exhibit cell cycle defects, including reduced population-doubling time and a delay in cell cycle reentry from quiescence, indicating that cyclin F plays a role in cell cycle regulation.
Department of Human and Molecular Genetics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
Michael T
MT
Tetzlaff
Chang
C
Bai
Milton
M
Finegold
John
J
Wilson
J Wade
JW
Harper
Kathleen A
KA
Mahon
Stephen J
SJ
Elledge
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D016213:Cyclins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D005313:Fetal Death / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010920:Placenta / Q000002:abnormalities*; D010929:Placentation; D011247:Pregnancy; D015183:Restriction Mapping; D014018:Tissue Distribution
C503669:CCNF protein, human; C503670:Ccnf protein, mouse; D016213:Cyclins; D018076:DNA, Complementary