• TNFRSF21, also known as DR6, belongs to the TNF superfamily receptor protein, which is highly expressed in lymphoid tissue, cerebellum, and some tumor cells. DR6 plays a role in regulating innate and acquired immune processes, and the knockout of this target can promote the development of Th2 cells. The related drugs are mainly monoclonal antibodies, the indication is multiple sclerosis, there are no drugs in the clinical stage, and there are few drugs under study.
• It may be used in the development and safety evaluation of drugs related to multiple sclerosis and airway inflammatory diseases.

Gene targeting strategy for B-hTNFRSF21 mice. The exons 2-3 of mouse Tnfrsf21 gene that encode extracellular domain are replaced by human counterparts in B-hTNFRSF21 mice. Other genes of  mice including 5 'UTR and 3' UTR are retained. The human TNFRSF21 expression is driven by endogenous mouse Tnfrsf21 promoter. 

Strain specific analysis of TNFRSF21 mRNA expression in wild-type C57BL/6 mice and B-hTNFRSF21 mice by RT-PCR. Brain RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hTNFRSF21 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human TNFRSF21 primers. Mouse TNFRSF21 mRNA was only detectable in wild-type mice. Human TNFRSF21 mRNA was exclusively detectable in homozygous B-hTNFRSF21 mice but not in wild-type mice. 

Western blot analysis of TNFRSF21 protein expression in homozygous B-hTNFRSF21 mice. Various tissue lysates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTNFRSF21 mice (H/H), and then analyzed by western blot with species-specific anti-TNFRSF21 antibody(CST, 93026). 40 μg total proteins were loaded for western blotting analysis. hTNFRSF21 was highly expressed in brain and cerebellum of humanized mice, but was less expressed in kidney, stomach and spleen. Red arrow: target protein.