Mice lacking cyclin D1 are small and show defects in eye and mammary gland development.
Using homologous recombination, mice lacking cyclin D1 were generated by replacing most of the first exon of the Cyl-1 gene with sequences encoding neomycin resistance. Cyl-1(-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 acinar 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 D1 kinase activity may facilitate G1 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.
Fantl
V
V
Laboratory of Viral Carcinogenesis, Imperial Cancer Research Fund (ICRF), London, UK.
Stamp
G
G
Andrews
A
A
Rosewell
I
I
Dickson
C
C
D000818:Animals; D001483:Base Sequence; D001824:Body Constitution / Q000235:genetics*; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D019938:Cyclin D1; D016213:Cyclins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D018390:Gene Targeting; D006579:Heterozygote; D006720:Homozygote; D007569:Jaw Abnormalities / Q000235:genetics; D008321:Mammary Glands, Animal / Q000002:abnormalities*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011995:Recombination, Genetic / Q000235:genetics; D012160:Retina / Q000002:abnormalities*; D013234:Stem Cells / Q000378:metabolism
D016213:Cyclins; D017931:DNA Primers; D015513:Oncogene Proteins; D019938:Cyclin D1