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Requirement for a functional Rb-1 gene in murine development

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Abstract

HUMAN retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal1 that they result from two mutational events, of which one is present in the germ line in hereditary cases, has been confirmed by more recent molecular analysis, which has shown both events to involve loss or mutational inactivation of the same gene, RB-1 (ref. 2). RB-1 heterozygosity also predisposes to osteosarcoma, and RB-1 allele losses are seen in sporadic lung, breast, prostate and bladder carcinomas3–7. RB-1 is expressed in most, if not all, tissues and codes for a nuclear phosphoprotein which becomes hypophosphorylated in the GO growth arrest state and in the Gl phase of the cell cycle2. To gain a further insight ino the role of RB-1 we and other groups8,9 have generated mice carrying an inactivated allele of the homologous gene, Rb-1 (ref. 10), by gene targeting11. We report here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency. However, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development. Broadly similar results are reported by the other groups8,9.

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Authors and Affiliations

  1. Cancer Research Campaign Laboratories, Department of Pathology, University of Edinburgh, Edinburgh, UK

    Alan R. Clarke & Martin L. Hooper

  2. AFRC Centre for Genome Research, University of Edinburgh, Edinburgh, UK

    Martin L. Hooper

  3. Division of Molecular Genetics, The Netherlands Cancer Institute and Department of Biochemistry, University of Amsterdam, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Els Robanus Maandag, Marian van Roon, Nathalie M. T. van der Lugt, Martin van der Valk, Anton Berns & Hein te Rielef

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  1. Alan R. Clarke
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  2. Els Robanus Maandag
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  3. Marian van Roon
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  4. Nathalie M. T. van der Lugt
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  5. Martin van der Valk
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  6. Martin L. Hooper
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  7. Anton Berns
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  8. Hein te Rielef
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Clarke, A., Maandag, E., van Roon, M. et al. Requirement for a functional Rb-1 gene in murine development. Nature 359, 328–330 (1992). https://doi.org/10.1038/359328a0

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