COP9 signalosome subunit 3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast.
Csn3 (Cops3) maps to the mouse chromosome 11 region syntenic to the common deletion interval for the Smith-Magenis syndrome, a contiguous gene deletion syndrome. It encodes the third subunit of an eight-subunit protein complex, the COP9 signalosome (CSN), which controls a wide variety of molecules of different functions. Mutants of this complex caused lethality at early development of both plants and Drosophila melanogaster. CSN function in vivo in mammals is unknown. We disrupted the murine Csn3 gene in three independent ways with insertional vectors, including constructing a approximately 3-Mb inversion chromosome. The heterozygous mice appeared normal, although the protein level was reduced. Csn3(-/-) embryos arrested after 5.5 days postcoitum (dpc) and resorbed by 8.5 dpc. Mutant embryos form an abnormal egg cylinder which does not gastrulate. They have reduced numbers of epiblast cells, mainly due to increased cell death. In the Csn3(-/-) mice, subunit 8 of the COP9 complex was not detected by immunohistochemical techniques, suggesting that the absence of Csn3 may disrupt the entire COP9 complex. Therefore, Csn3 is important for maintaining the integrity of the COP9 signalosome and is crucial to maintain the survival of epiblast cells and thus the development of the postimplantation embryo in mice.
Yan
Jiong
J
Department of Molecular and Human Genetics, Texas Children's Hospital, Houston, Texas 77030, USA.
Walz
Katherina
K
Nakamura
Hisashi
H
Carattini-Rivera
Sandra
S
Zhao
Qi
Q
Vogel
Hannes
H
Wei
Ning
N
Justice
Monica J
MJ
Bradley
Allan
A
Lupski
James R
JR
D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000502:physiology; D000075686:COP9 Signalosome Complex; D002455:Cell Division / Q000502:physiology*; D002678:Chimera; D007446:Chromosome Inversion; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D010447:Peptide Hydrolases; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013737:Testis / Q000378:metabolism
C000618791:Cops3 protein, mouse; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex