Delayed early embryonic lethality following disruption of the murine cyclin A2 gene.
In higher eukaryotes, cell cycle progression is controlled by cyclin dependent kinases (Cdks) complexed with cyclins. A-type cyclins are involved at both G1/S and G2/M transitions of the cell cycle. Cyclin A2 activates cdc2 (Cdk1) on passage into mitosis and Cdk2 at the G1/S transition. Antisense constructs, or antibodies directed against cyclin A2 block cultured mammalian cells at both of these transitions. In contrast, overexpression of cyclin A2 appears to advance S phase entry and confer anchorage-independent growth, and can lead to apoptosis. A second A-type cyclin, cyclin A1 has been described recently which, in the mouse, is expressed in germ cells but not somatic tissues. To address the possible redundancy between different cyclins in vivo and also the control of early embryonic cell cycles, we undertook the targeted deletion of the murine cyclin A2 gene. The homozygous null mutant is embryonically lethal, demonstrating that the cyclin A2 gene is essential. Surprisingly, homozygous null mutant embryos develop normally until post-implantation, around day 5.5 p.c. This observation may be explained by the persistence of a maternal pool of cyclin A2 protein until at least the blastocyst stage, or an unexpected role for cyclin A1 during early embryo development.
Murphy
M
M
Institut National de la Santé et de la Recherche Médicale, Unité 370, Faculté Necker, Paris, France.
Stinnakre
M G
MG
Senamaud-Beaufort
C
C
Winston
N J
NJ
Sweeney
C
C
Kubelka
M
M
Carrington
M
M
Bréchot
C
C
Sobczak-Thépot
J
J
D000818:Animals; D001755:Blastocyst / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D019925:Cyclin A; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005313:Fetal Death / Q000235:genetics; D018390:Gene Targeting; D005804:Genes, Lethal; D008297:Male; D051379:Mice; D013234:Stem Cells
D019925:Cyclin A; D016213:Cyclins