Dll1-flox Mouse

Dll1, Delta-like 1, is a ligand for the Notch receptor and is crucial in multiple biological processes. The Notch signaling pathway, in which Dll1 participates, is fundamental for brain morphogenesis, T-cell development, angiogenesis, and tissue homeostasis [1,4,3,5]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying Dll1's functions.

In neurodevelopment, heterozygous pathogenic DLL1 variants in humans cause variable neurodevelopmental phenotypes including intellectual disability, autism spectrum disorder, and seizures, supporting haploinsufficiency as a pathogenesis mechanism [1]. In mice, Dll1 haploinsufficiency leads to brain abnormalities like microcephaly, hydrocephalus, reduced neural cell density, and myelination changes, causing mild neurological deficits [2]. In the thymus, Dll1 can function as a ligand for Notch1 and Notch2, restoring T-cell development defects in Dll4-deficient conditions [4]. In the meniscus, the DLL1/NOTCH1 signaling pathway is vital for maintaining angiogenesis, as its lack leads to vascular decline during development and degeneration [3].

In conclusion, Dll1 plays essential roles in neurodevelopment, T-cell development, and angiogenesis. Studies using KO and CKO mouse models have significantly contributed to understanding its functions in these processes, with implications for related diseases such as neurodevelopmental disorders and meniscus-associated pathologies.