hCD38 Mouse

The CD38 gene, located on human chromosome 4, encodes a multifunctional type II transmembrane glycoprotein (also known as ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1) that acts both as an ectoenzyme and a receptor. It is widely expressed on immune cells, including plasma cells, activated T and B lymphocytes, natural killer cells, monocytes, and dendritic cells, with variable expression depending on cell activation and differentiation states; it is also found in various tissues and can exist in soluble forms ^[1]. The encoded protein primarily functions as a potent NADase, catalyzing the hydrolysis of NAD⁺ to ADP-ribose (ADPR) and nicotinamide while also synthesizing cyclic ADP-ribose (cADPR), a second messenger involved in intracellular calcium mobilization, cell adhesion (via CD31 interaction), signal transduction, and metabolic regulation ^[2-4]. High CD38 expression labels malignant plasma cells in multiple myeloma and serves as a prognostic marker in chronic lymphocytic leukemia (CLL), while its role in NAD⁺ depletion links it to inflammation, aging, immune modulation, and metabolic diseases ^[5-6]. In drug development, CD38 has emerged as a major target, with approved monoclonal antibodies like daratumumab (and isatuximab) demonstrating efficacy in multiple myeloma through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptosis induction, with ongoing studies exploring broader applications in hematologic malignancies and autoimmune conditions ^[7].

The hCD38 mice were a humanized mouse model generated via gene editing. The mouse Cd38 endogenous splice acceptor (SA) of intron 1 was replaced with the human CD38 SA of intron 1-Human CD38 exon 2~8 CDS-WPRE-BGH pA cassette. This model is primarily indicated for mechanistic studies and therapeutic development in hematologic malignancies such as multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), as well as for the development of CD38-targeted agents. Furthermore, given the pivotal role of CD38 in NAD⁺ metabolism, this model is also suitable for evaluating the efficacy of CD38-targeted therapies in ameliorating age-related metabolic decline, neurodegenerative diseases, and enhancing NAD⁺ levels.