Abstract
Oligosyndactylism (Os) is a radiation-induced mutation on mouse chromosome 8 associated with early postimplantation lethality in homozygotes and abnormal development of the limbs and kidneys in heterozygotes. The recessive lethal effect of Os is due to a mitotic block of the embryonic cells that becomes apparent at the blastocyst stage, but it is not known if the heterozygous effect of Os is due to haploinsufficiency of the gene responsible for the mitotic arrest, or is due to mutation(s) of other gene(s). We have recently described a transgene-induced recessive mutation, 94-A/K, that results in early postimplantation death of the embryos, and we have mapped this mutation to the same region of chromosome 8 where Os has been assigned. On the basis of complementation tests between transgenic and Os/+ mice, in vitro growth characteristics and increased mitotic index of 94-A/K embryos, and molecular structural analysis of 94-A and 94-K transgenic and Os/+ mice, we conclude that the 94-A/K mutation represents a new allele of Os. This insertional mutation should facilitate the isolation of a mammalian gene essential for normal progression of the cell cycle beyond metaphase.
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- Campbell M. S., Gorbsky G. J. Microinjection of mitotic cells with the 3F3/2 anti-phosphoepitope antibody delays the onset of anaphase. J Cell Biol. 1995 Jun;129(5):1195–1204. doi: 10.1083/jcb.129.5.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desai A., Mitchison T. J. A new role for motor proteins as couplers to depolymerizing microtubules. J Cell Biol. 1995 Jan;128(1-2):1–4. doi: 10.1083/jcb.128.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fitzgerald P. H., Pickering A. F., Mercer J. M., Miethke P. M. Premature centromere division: a mechanism of non-disjunction causing X chromosome aneuploidy in somatic cells of man. Ann Hum Genet. 1975 May;38(4):417–428. doi: 10.1111/j.1469-1809.1975.tb00631.x. [DOI] [PubMed] [Google Scholar]
- Gallant P., Nigg E. A. Cyclin B2 undergoes cell cycle-dependent nuclear translocation and, when expressed as a non-destructible mutant, causes mitotic arrest in HeLa cells. J Cell Biol. 1992 Apr;117(1):213–224. doi: 10.1083/jcb.117.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonda M. A., Hsu Y. C. Correlative scanning electron, transmission electron, and light microscopic studies of the in vitro development of mouse embryos on a plastic substrate at the implantation stage. J Embryol Exp Morphol. 1980 Apr;56:23–39. [PubMed] [Google Scholar]
- Gorbsky G. J., Sammak P. J., Borisy G. G. Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends. J Cell Biol. 1987 Jan;104(1):9–18. doi: 10.1083/jcb.104.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartwell L. H., Kastan M. B. Cell cycle control and cancer. Science. 1994 Dec 16;266(5192):1821–1828. doi: 10.1126/science.7997877. [DOI] [PubMed] [Google Scholar]
- Hartwell L. H., Weinert T. A. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989 Nov 3;246(4930):629–634. doi: 10.1126/science.2683079. [DOI] [PubMed] [Google Scholar]
- Hiraoka L., Golden W., Magnuson T. Spindle-pole organization during early mouse development. Dev Biol. 1989 May;133(1):24–36. doi: 10.1016/0012-1606(89)90293-5. [DOI] [PubMed] [Google Scholar]
- Holloway S. L., Glotzer M., King R. W., Murray A. W. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell. 1993 Jul 2;73(7):1393–1402. doi: 10.1016/0092-8674(93)90364-v. [DOI] [PubMed] [Google Scholar]
- Hoyt M. A., Totis L., Roberts B. T. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell. 1991 Aug 9;66(3):507–517. doi: 10.1016/0092-8674(81)90014-3. [DOI] [PubMed] [Google Scholar]
- Irniger S., Piatti S., Michaelis C., Nasmyth K. Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell. 1995 Apr 21;81(2):269–278. doi: 10.1016/0092-8674(95)90337-2. [DOI] [PubMed] [Google Scholar]
- Jordan M. A., Thrower D., Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci. 1992 Jul;102(Pt 3):401–416. doi: 10.1242/jcs.102.3.401. [DOI] [PubMed] [Google Scholar]
- King R. W., Jackson P. K., Kirschner M. W. Mitosis in transition. Cell. 1994 Nov 18;79(4):563–571. doi: 10.1016/0092-8674(94)90542-8. [DOI] [PubMed] [Google Scholar]
- Kung A. L., Sherwood S. W., Schimke R. T. Cell line-specific differences in the control of cell cycle progression in the absence of mitosis. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9553–9557. doi: 10.1073/pnas.87.24.9553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamb J. R., Michaud W. A., Sikorski R. S., Hieter P. A. Cdc16p, Cdc23p and Cdc27p form a complex essential for mitosis. EMBO J. 1994 Sep 15;13(18):4321–4328. doi: 10.1002/j.1460-2075.1994.tb06752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li R., Murray A. W. Feedback control of mitosis in budding yeast. Cell. 1991 Aug 9;66(3):519–531. doi: 10.1016/0092-8674(81)90015-5. [DOI] [PubMed] [Google Scholar]
- Mayer-Jaekel R. E., Ohkura H., Gomes R., Sunkel C. E., Baumgartner S., Hemmings B. A., Glover D. M. The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase. Cell. 1993 Feb 26;72(4):621–633. doi: 10.1016/0092-8674(93)90080-a. [DOI] [PubMed] [Google Scholar]
- McIntosh J. R., Koonce M. P. Mitosis. Science. 1989 Nov 3;246(4930):622–628. doi: 10.1126/science.2683078. [DOI] [PubMed] [Google Scholar]
- Minshull J., Sun H., Tonks N. K., Murray A. W. A MAP kinase-dependent spindle assembly checkpoint in Xenopus egg extracts. Cell. 1994 Nov 4;79(3):475–486. doi: 10.1016/0092-8674(94)90256-9. [DOI] [PubMed] [Google Scholar]
- Mitchison T., Evans L., Schulze E., Kirschner M. Sites of microtubule assembly and disassembly in the mitotic spindle. Cell. 1986 May 23;45(4):515–527. doi: 10.1016/0092-8674(86)90283-7. [DOI] [PubMed] [Google Scholar]
- Murray A. W. Creative blocks: cell-cycle checkpoints and feedback controls. Nature. 1992 Oct 15;359(6396):599–604. doi: 10.1038/359599a0. [DOI] [PubMed] [Google Scholar]
- Murray A. W. The genetics of cell cycle checkpoints. Curr Opin Genet Dev. 1995 Feb;5(1):5–11. doi: 10.1016/s0959-437x(95)90046-2. [DOI] [PubMed] [Google Scholar]
- Murray A. Cyclin ubiquitination: the destructive end of mitosis. Cell. 1995 Apr 21;81(2):149–152. doi: 10.1016/0092-8674(95)90322-4. [DOI] [PubMed] [Google Scholar]
- Paterson H. F. In vivo and in vitro studies on the early embryonic lethal oligosyndactylism (Os) in the mouse. J Embryol Exp Morphol. 1979 Aug;52:115–125. [PubMed] [Google Scholar]
- Pravtcheva D. D., Adra C. N., Ruddle F. H. Timing of paternal Pgk-1 expression in embryos of transgenic mice. Development. 1991 Apr;111(4):1109–1120. doi: 10.1242/dev.111.4.1109. [DOI] [PubMed] [Google Scholar]
- Pravtcheva D. D., Wise T. L. A postimplantation lethal mutation induced by transgene insertion on mouse chromosome 8. Genomics. 1995 Dec 10;30(3):529–544. doi: 10.1006/geno.1995.1274. [DOI] [PubMed] [Google Scholar]
- Rieder C. L., Cole R. W., Khodjakov A., Sluder G. The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol. 1995 Aug;130(4):941–948. doi: 10.1083/jcb.130.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rieder C. L., Palazzo R. E. Colcemid and the mitotic cycle. J Cell Sci. 1992 Jul;102(Pt 3):387–392. doi: 10.1242/jcs.102.3.387. [DOI] [PubMed] [Google Scholar]
- Rudd N. L., Teshima I. E., Martin R. H., Sisken J. E., Weksberg R. A dominantly inherited cytogenetic anomaly: a possible cell division mutant. Hum Genet. 1983;65(2):117–121. doi: 10.1007/BF00286646. [DOI] [PubMed] [Google Scholar]
- Yee D., Golden W., Debrot S., Magnuson T. Short-term rescue by RNA injection of a mitotic arrest mutation that affects the preimplantation mouse embryo. Dev Biol. 1987 Jul;122(1):256–261. doi: 10.1016/0012-1606(87)90350-2. [DOI] [PubMed] [Google Scholar]