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Publication : Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice.

First Author  Maandag EC Year  1994
Journal  EMBO J Volume  13
Issue  18 Pages  4260-8
PubMed ID  7925271 Mgi Jnum  J:20542
Mgi Id  MGI:68628 Doi  10.1002/j.1460-2075.1994.tb06746.x
Citation  Maandag EC, et al. (1994) Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice. EMBO J 13(18):4260-8
abstractText  The requirement for a functional retinoblastoma gene, Rb-1, in murine development around days 12-15 of gestation precludes monitoring the effect of loss of Rb-1 function on later stages of development and on tumorigenesis in adult mice. Here we describe the developmental rescue of embryonic stem cells carrying two inactive Rb-1 alleles in chimeric mice. Rb-1- cells contributed substantially to most tissues in adult chimeras, including blood, liver and central nervous system, which were severely affected in pure Rb-1- embryos. The adult chimeric erythroid compartment appeared completely normal, but an increased number of nucleated red cells was observed during fetal liver erythropoiesis in highly chimeric embryos. No ostensive abnormalities were seen in the developing and adult CNS. However, the developing retina of chimeric Rb-1- embryos showed ectopic mitoses and substantial cell degeneration, while the contribution of Rb-1- cells to the adult retina was much reduced. Moreover, the formation of lens fibre cells was severely disturbed. No retinoblastomas developed in any of these mice. Instead, nearly all animals died of pituitary gland tumours which were exclusively derived from Rb-1- cells.
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