ENPP3: ENPP3, also known as CD203c, is a type II transmembrane ectonucleotidase of the ENPP family. 

• Gene Information: ENPP3, also known as CD203c, is a type II transmembrane ectonucleotidase of the ENPP family. It belongs to the ENPP family and hydrolyzes extracellular nucleotides. 
• Protein Expression: ENPP3 is expressed on basophils, mast cells, and subsets of epithelial cells under normal conditions. It is overexpressed in several malignancies, including renal cell carcinoma and certain gastrointestinal cancers, making it an attractive therapeutic target. 
• Signaling Pathway: ENPP3 hydrolyzes extracellular nucleotides to regulate purinergic signaling and the tumor microenvironment. Its activity influences cell proliferation, immune responses, and tumor progression. 
• Therapeutic Inhibition: ENPP3-targeted antibodies and ADCs selectively eliminate ENPP3-positive tumor cells and are under clinical development.

ENPP3 

• Exons 2-25 of mouse ENPP3 gene that extracellular domain are replaced by human counterparts in B-hENPP3 mice. 
• The promoter and 5’ and 3’ UTR, transmembrane domain, cytoplasmic region  region of the mouse gene are retained. The human ENPP3 expression is driven by endogenous mouse Enpp3 promoter, while mouse ENPP3 gene transcription and translation will be disrupted.

• Mouse ENPP3 mRNA was detectable only in kidney of wild-type C57BL/6 mice. 
• Human ENPP3 mRNA was detectable only in homozygous B-hENPP3 mice, but not in wild-type mice.

mRNA ENPP3 were detectable in B-hENPP3 mice by RT-PCR and sequencing. Kidney tissues were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hENPP3 mice (H/H). Primers were designed to detect the human and mouse ENPP3. Sequencing of the PCR products confirmed that the amplified sequences were consistent with database reference sequences.

• Human ENPP3 was detected in the stomach, small intestine, colon and kidney of homozygous B-hENPP3 mice, but not in C57BL/6 mice.

Immunohistochemical (IHC) analysis of ENPP3 protein expression in wild-type mice and B-hENPP3 mice. Major tissues were collected from wild-type mice and homozygous B-hENPP3 mice and analyzed by IHC with anti-ENPP3 antibody (Abcam, ab313376).