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Requirement for a functional Rb-1 gene in murine development.

TitleRequirement for a functional Rb-1 gene in murine development.
Publication TypeJournal Article
Year of Publication1992
AuthorsClarke AR, Maandag ER, van Roon M, van der Lugt NM, van der Valk M, Hooper ML, Berns A, H Riele te
Date Published1992 Sep 24
KeywordsAbnormalities, Multiple, Animals, Cells, Cultured, Chimera, Chromosome Mapping, Crosses, Genetic, Embryonic and Fetal Development, Exons, Genes, Retinoblastoma, Hematopoiesis, Humans, Mice, Mice, Inbred Strains, Stem Cells

Human retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal 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 carcinomas. RB-1 is expressed in most, if not all, tissues and codes for a nuclear phosphoprotein which becomes hypophosphorylated in the G0 growth arrest state and in the G1 phase of the cell cycle. To gain a further insight into the role of RB-1 we and other groups have generated mice carrying an inactivated allele of the homologous gene, Rb-1 (ref. 10), by gene targeting. 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 groups.

Alternate JournalNature
PubMed ID1406937