Cul3 is required for normal development of the mammary gland. 2021

Cristina M Cummings, and Jeffrey D Singer
School of Natural Sciences and Mathematics, Stockton University, Galloway, NJ, USA.

Cullin 3 (Cul3) has recently been implicated in a multitude of different processes, including the oxidative stress response, autophagy, tumorigenesis, and differentiation. To investigate the role of Cul3 in mammary gland development, we created a mouse model system using Cre-lox targeting where Cul3 is specifically deleted from the mammary gland. Such MMTV-Cre Cul3Flx/Flx mice examined at 2 and 3 months of age show delays and defects in mammary gland development. Mammary ductal trees from Cul3-deficient mammary glands exhibit delayed forward growth through the mammary fat pad, dilation of the ducts, and abnormal morphology of some of the epithelial structures within the gland. Additionally, terminal end buds are larger and less plentiful in MMTV-Cre Cul3Flx/Flx mammary glands, and there is significantly less primary and secondary branching compared to control animals. In contrast, by 6 months of age, the mammary ductal tree has grown to fill the entire mammary fat pad in glands lacking Cul3. However, distorted epithelial structures and dilated ducts persist. MMTV-Cre Cul3Flx/Flx mothers are able to nourish their litters, but the process of involution is slightly delayed in mammary glands lacking Cul3. Therefore, we conclude that while Cul3 is not essential for mammary gland function, Cul3 is required for the mammary gland to proceed normally through development.

UI MeSH Term Description Entries
D008321 Mammary Glands, Animal MAMMARY GLANDS in the non-human MAMMALS. Mammae,Udder,Animal Mammary Glands,Animal Mammary Gland,Mammary Gland, Animal,Udders
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D044842 Cullin Proteins A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES. Cullin,Cullin Domain Protein,Cullin Domain Proteins,Cullin Protein,Cullins
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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