• TNFRSF19 (TROY/TAJ) is a receptor primarily expressed in the nervous system that participates in neural development, immune modulation, and tissue homeostasis through the NF-κB/JNK signaling pathway. Its overexpression is strongly associated with cancers such as glioblastoma, making it a potential target for anticancer therapy, with drug development (e.g., antibodies and inhibitors) currently in the preclinical stage.
• The exons 3-6 of mouse Tnfrsf19 gene that encode extracellular domain was replaced by human counterparts in B-hTNFRSF19 mice. The genomic region of mouse Tnfrsf19 gene that transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric TNFRSF19 expression was driven by endogenous mouse Tnfrsf19 promoter, while mouse Tnfrsf19 gene transcription and translation will be disrupted.
• TNFRSF19 was detected in lung, skin and kidney in from wild-type mice and homozygous B-hTNFRSF19 mice, the antibody was cross-reactive between human and mouse.
• Mouse Tnfrsf19 mRNA were detectable only in wild-type C57BL/6JNifdc mice. Human TNFRSF19 mRNA was detectable only in homozygous B-hTNFRSF19 mice but not in wild-type mice.
• B-hTNFRSF19 mice can be used to study the in vivo efficacy and safety evaluation of drugs.

Gene targeting strategy for B-hTNFRSF19 mice. The exons 3-6 of mouse Tnfrsf19 gene that encode extracellular domain was replaced by human counterparts in B-hTNFRSF19 mice. The genomic region of mouse Tnfrsf19 gene that transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric TNFRSF19 expression was driven by endogenous mouse Tnfrsf19 promoter, while mouse Tnfrsf19 gene transcription and translation will be disrupted.

Western blot analysis of TNFRSF19 protein expression in homozygous B-hTNFRSF19 mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hTNFRSF19 mice (H/H), and then analyzed by western blot with anti-TNFRSF19 antibody (Invitrogen, MA5-37871). 40 μg total proteins were loaded for western blotting analysis. TNFRSF19 was detected in lung, skin and kidney in from wild-type mice and homozygous B-hTNFRSF19 mice, the antibody was cross-reactive between human and mouse.

Strain specific analysis of TNFRSF19 mRNA expression in wild-type C57BL/6JNifdc mice and B-hTNFRSF19 mice by RT-PCR. Lung RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hTNFRSF19 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human TNFRSF19 primers. Mouse Tnfrsf19 mRNA were detectable only in wild-type C57BL/6JNifdc mice. Human TNFRSF19 mRNA was detectable only in homozygous B-hTNFRSF19 mice but not in wild-type mice.