Dlk1-KO Mouse

DLK1, also known as delta-like canonical notch ligand 1, is a maternally imprinted, paternally expressed gene encoding a transmembrane protein. It is a non-canonical NOTCH ligand and plays significant roles in adipose tissue homeostasis, neurogenesis, stem cell pool regulation, and tissue differentiation [1,3]. It is located in the imprinted chromosome 14q32 region, and its deregulation is associated with developmental disorders like Temple syndrome [1,4].

In terms of disease-related findings, paternally inherited genetic defects of DLK1 were identified in families with nonsyndromic central precocious puberty (CPP) and a metabolic phenotype, suggesting its role in modulating the hypothalamic-pituitary-gonadal axis [1]. In neuroblastoma, high expression of DLK1 directly correlates with a super-enhancer, and its silencing leads to increased cellular differentiation. An antibody-drug conjugate targeting DLK1 shows potent cytotoxicity in xenograft models, indicating its potential as an immunotherapeutic target [2]. In adrenocortical carcinoma, DLK1 is a prognostic marker, and its cleavable ectodomain in serum can aid in diagnosis [5]. Also, in hepatocellular carcinoma, DLK1-directed chimeric antigen receptor T-cell therapy can specifically eliminate DLK1-positive cancer cells [6].

In conclusion, DLK1 is crucial for multiple biological processes and is associated with various diseases. Studies on genetic defects and expression patterns in different disease models, such as in CPP, neuroblastoma, adrenocortical carcinoma, and hepatocellular carcinoma, have revealed its significance in disease development and its potential as a therapeutic target. Understanding DLK1 may provide new strategies for treating these diseases.