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Mice lacking cyclin D1 are small and show defects in eye and mammary gland development
1Laboratory of Viral Carcinogenesis, Imperial Cancer Research Fund (ICRF), London, UK.
Abstract:
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.
Insights
Mice lacking cyclin D1 (Cyl-1) were viable but smaller, with severe retinopathy and mammary gland defects. Cyclin D1 is not essential for most tissue development, but crucial for specific cell lineages.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Cyclin D1 is a key regulator of the cell cycle.
- Its precise role in mammalian development is not fully understood.
Purpose of the Study:
- To investigate the physiological and developmental consequences of cyclin D1 deficiency in mice.
Main Methods:
- Generation of cyclin D1-deficient (Cyl-1-/-) mice using homologous recombination.
- Phenotypic analysis of nullizygous mice, including developmental assessments and cell-cycle studies.
Main Results:
- Cyl-1-/- mice were viable and fertile but exhibited reduced size.
- Significant abnormalities observed include severe retinopathy and impaired mammary gland development with lactation failure.
- Jaw malformations affecting incisor alignment occurred in approximately 50% of nullizygous animals.
- Mouse embryo fibroblasts from Cyl-1-/- embryos showed normal cell-cycle progression.
Conclusions:
- Cyclin D1 kinase activity is not essential for the development of most tissues and organs.
- Specific cell lineages, such as those in the retina and mammary gland, are highly sensitive to the absence of cyclin D1.
- Cyclin D1 plays a critical, albeit specialized, role in mammalian development.