These Ccnd1 knock-out mice exhibit growth retardation with abnormal neurological, retinal, and mammary gland development.
Robert Weinberg, Whitehead Institute (MIT)
Mice homozygous for the targeted mutation develop to term but show growth retardation that is most pronounced by three weeks of age. The majority of mutant mice die early in life, often within the first month. Survivors continue to show lower than average weight and increased mortality. Mammary gland epithelial duct development is normal in virgin mutant mice. Mutant females that survive to adulthood are fertile, but mammary glands of pregnant mice show a dramatic impairment in the expansion of alveolar lobes and mice are unable to lactate. Steroid hormone levels are normal, and there is no apparent defect in estrogen receptor number, suggesting that cyclin D1 deficiency has an effect on the target tissue directly. Mutant mice demonstrate a neurological abnormality evidenced by limb retraction when lifted by their tails. The most severely affected animals remain in a clasped, flexed position for a few seconds after they have been returned to their cage. Retinal abnormalities include a dramatic reduction in cell numbers in all cell layers of the neural retina. This is due to the severely reduced ability of mutant retinal cell precursors to proliferate during embryonic development. The thickness of the inner plexiform layer is also reduced. The cells within the retina respond properly to light.
A 3700 bp EagI fragment of the mouse cyclin D1 gene, (5' to the first coding exon) was used in the targeting vector, and electoporated into D3 ES cells. Cyclin D1 heterozygous ES cells ere injected into C57BL/6 embryos, and the resulting chimeras were bred to B6 mice. The resulting cyclin D1 heterozygotes were bred to produce homozygous mice. The targeting vector deletes coding portions of exons I-III of the cyclin D1 gene and replaces them with the neomycin resistance gene.
|Allele Name||targeted mutation 1, Robert A Weinberg|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD1-; cyclin D1-|
|Gene Symbol and Name||Ccnd1, cyclin D1|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A genomic fragment containing part of exon 1, exon 2 and exon 3 was replaced with a neomycin selection cassette. The deleted sequences encode the cyclin box domain thought to be required for protein activity. Western blot analysis on embryonic fibroblasts derived from homozygous mice confirmed that no stable protein was made from this allele.|
|Mutations Made By|| |
Robert Weinberg, Whitehead Institute (MIT)
When maintaining a live colony, heterozygous mice may be bred together. Some homozygous mice die within first month.
When using the cyclin D1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002537 in your Materials and Methods section.
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