hCD38 Mouse
Product Name
hCD38 Mouse
Product ID
C002047
Strain Name
C57BL/6NCya-Cd38em1(hCD38)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “hCD38 Mouse (Catalog C002047) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CD38
Gene Alias
ADPRC1, cADPR1, ADPRC 1
NCBI ID
Chromosome
Chr 4 (Human)
MGI ID
Datasheet
Strain Description
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.
Reference
Piedra-Quintero ZL, Wilson Z, Nava P, Guerau-de-Arellano M. CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Front Immunol. 2020 Nov 30;11:597959.
Tohgo A, Takasawa S, Noguchi N, Koguma T, Nata K, Sugimoto T, Furuya Y, Yonekura H, Okamoto H. Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38. J Biol Chem. 1994 Nov 18;269(46):28555-7.
Takasawa S, Tohgo A, Noguchi N, Koguma T, Nata K, Sugimoto T, Yonekura H, Okamoto H. Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP. J Biol Chem. 1993 Dec 15;268(35):26052-4.
Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, Dianzani U, Stockinger H, Malavasi F. Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member. J Immunol. 1998 Jan 1;160(1):395-402.
Brachtl G, Piñón Hofbauer J, Greil R, Hartmann TN. The pathogenic relevance of the prognostic markers CD38 and CD49d in chronic lymphocytic leukemia. Ann Hematol. 2014 Mar;93(3):361-74.
García-Guerrero E, Götz R, Doose S, Sauer M, Rodríguez-Gil A, Nerreter T, Kortüm KM, Pérez-Simón JA, Einsele H, Hudecek M, Danhof S. Publisher Correction: Upregulation of CD38 expression on multiple myeloma cells by novel HDAC6 inhibitors is a class effect and augments the efficacy of daratumumab. Leukemia. 2022 Jan;36(1):297. doi: 10.1038/s41375-021-01355-6. Erratum for: Leukemia. 2021 Jan;35(1):201-214.
Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, Syed K, Liu K, van de Donk NW, Weiss BM, Ahmadi T, Lokhorst HM, Mutis T, Sasser AK. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016 Jul 21;128(3):384-94.
Strain Strategy
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.
Figure 1. Gene editing strategy for hCD38 mice.
Application Area
Screening, development, and safety evaluation of CD38-targeted therapeutics;
Mechanistic exploration and therapeutic development for malignant hematologic tumors, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL);
Efficacy assessment regarding age-related metabolic decline, neurodegenerative diseases, and the elevation of NAD⁺ levels.
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