Using homologous recombination, mice lacking cyclin Dl were generated by replacing most of the first exon of the Cyl-1 gene with sequences encoding neomycin resistance. Cyl-1~'~ mice were viable and fertile but consistently smaller than their heterozygous or wild-type littermates. The nullizygous animals also showed two distinctive abnormalities: a severe retinopathy caused by impaired development of all layers of the retina and, in the mammary gland during pregnancy, a marked reduction in

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... r development accompanied by a failure to lactate. Approximately 50% of animals also had a malformation of the jaw that manifested itself as a misalignment of the incisor teeth. Mouse embryo fibroblasts isolated from 14 day nullizygous, heterozygous, or wild-type embryos and grown under standard conditions showed similar cell-cycle and growth characteristics. Thus although cyclin Dl kinase activity may facilitate G, progression, it is not essential for the development of most tissues and organs, and only a few specialized cell lineages are demonstrably sensitive to its absence. -Published by genesdev.cshlp.org Downloaded from Access the most recent version at doi: 9: 1995, Genes Dev. V Fantl, G Stamp, A Andrews, et al. mammary gland development. Mice lacking cyclin D1 are small and show defects in eye and References http://genesdev.cshlp.org/content/9/19/2364.full.html#ref-list-1