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Effects of Dll1 blocking antibody on gene expression profiles of the brachiocephalic arteries in ApoE-deficient mice fed a high-fat diet

ABSTRACT: To examine the effects of Dll1 blocking antibody (Dll1 Ab) on gene expression profiles of the brachiocephalic arteries, ApoE-deficient mice were fed a high-fat diet from 12 weeks of age. Dll1 Ab or control non-immune IgG was intraperitoneally injected from 20 weeks of age. At 32 weeks of age, brachiocephalic arteries were excised, and gene expressions were evaluated.

ORGANISM(S): Mus musculus

PROVIDER: GSE275793 | GEO | 2025/08/27

REPOSITORIES: GEO

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Project description:BACKGROUND: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized. CONCLUSIONS/SIGNIFICANCE: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes. Four organs (liver, spleen, thymus, brain) of the Dll1 mutant mouse line analysed by cDNA microarray technology. Experiments include four biological replicates for reference (wildtype) and mutant animals. Two technical replicates for each mutant mouse were performed. As reference pooled RNA of the same organ was used. 50% of the chip hybridisations are dye sway experiments.

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Effects of Dll1 blocking antibody on gene expression profiles of the brachiocephalic arteries in ApoE-deficient mice fed a high-fat diet

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