Inactivation of the mouse Brca1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development.

Genes and Development - Tập 10 Số 14 - Trang 1835-1843 - 1996
Chia‐Yang Liu1, Andrea Flesken‐Nikitin1, S Li1, Yanwu Zeng1, W H Lee1
1Center for Molecular Medicine/Institute of Biotechnology, The University of Texas Health Science Center at San Antonio 78245, USA.

Tóm tắt

BRCA1 is proposed to be a tumor suppressor gene. To explore the biological function of BRCA1, a partial deletion (amino acids 300-361) of mouse Brca1 exon 11 was introduced into the genome of embryonic stem (ES) cells by homologous recombination. Mice carrying one mutated allele of Brca1 appear normal and are fertile up to 10 months of age without any sign of illness. However, no viable progeny homozygous for the Brca1 mutant allele were obtained. Detailed analysis of large numbers of embryos at different stages of development indicated that the homozygous mutant concepti are severely retarded in growth as early as embryonic day 4.5 (E4.5) and are resorbed completely by E8.5. Although the homozygotes at E5.5-E6.5 are able to synthesize DNA and display distinguishable embryonic and extraembryonic structures, they fail to differentiate and form egg cylinders. Consequently, they were unable to form primitive streaks and undergo gastrulation. Consistent with these in vivo results, blastocysts homozygous for mutated Brca1 alleles are at a considerable disadvantage when grown in vitro. These observations suggest that Brca1 has an important role in the early development of mouse embryos.

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Tài liệu tham khảo

10.1002/1097-0142(19930701)72:1<114::AID-CNCR2820720122>3.0.CO;2-0

1995, A human BRCA1 gene knockout., Nature, 375, 541, 10.1038/375541b0

1995, Inactivation of Myf-6 and Myf-5 genes in mice leads to alternations in skeletal muscle development., EMBO J., 14, 1176, 10.1002/j.1460-2075.1995.tb07101.x

Bradley, A. 1987. Production and analysis of chimeras. In Teratocarcinomas and embryonic stem cells: A practical approach (ed. E.f. Robertson), pp. 113–151. IRL Press, Oxford, UK.

1995, Aberrant subcellular localization of BRCA1 in breast cancer., Science, 270, 789, 10.1126/science.270.5237.789

Chen, Y., Farmer, A.A. Chen, C.-F. Jones, D.C. Chen, P.-L. and Lee. W.-H. 1996. BRCA1 is a 220 kDa nuclear phosphopro-tein that is expressed and phosphorylated in a cell cycle dependent manner. Cancer Research (in press).

10.1101/gad.8.3.265

10.1101/gad.8.24.3045

10.1126/science.7939630

10.1038/ng0296-191

10.1126/science.2270482

10.1007/BF00376364

10.1016/0012-1606(79)90217-3

1981, The molecular and cellular basis of preimplantation mouse development., Biol. Rev., 56, 463, 10.1111/j.1469-185X.1981.tb00356.x

Kaufman, M.H. 1992. The atlas of mouse development. Academic Press, London, UK.

10.1073/pnas.68.4.820

10.1093/nar/19.15.4293

10.1101/gad.9.21.2712

10.1038/359228a0

10.1101/gad.8.17.2008

10.1038/ng0995-17

10.1126/science.7545954

10.1016/S0092-8674(00)81073-9

1995, Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome., Development, 121, 3347, 10.1242/dev.121.10.3347

10.1146/annurev.cb.10.110194.000245

Robertson, E.J. 1987. Embryo-derived stem cells. In Teratocarcinomas and embryonic stem cells: A practical approach. (ed. E.J. Robertson), pp. 71–112. IRL Press, Oxford, UK.

Sambrook, J., E.F. Fritsch, and T. Maniatis. 1989. Molecular cloning: A laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

10.1038/294450a0

10.1093/jnci/86.24.1860

1985, Embryonic axis orientation in the mouse and its correlation with blastocyst relationships to the uterus II. Relationship from 4 ¼ to 9 ½ days., J. Embryol. Exp. Mor-phol., 89, 15

10.1038/ng1092-128

10.1016/0092-8674(91)90499-O

10.1101/gad.8.16.1949

10.1136/bmj.305.6858.855

10.1101/gad.8.24.3032

10.1101/gad.9.11.1388

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Genes and Development

Tập 10 Số 14

1835-1843

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