• DR3 is a cell surface receptor that belongs to the tumor necrosis factor receptor superfamily and plays a role in apoptosis, immune regulation, and inflammatory responses.
• FcRn is an IgG antibody receptor located on the cell membrane that can bind to the Fc region of IgG and serum albumin. It is recycled back into the circulatory system for reuse, preventing the degradation of IgG molecules and albumin by lysosomes, thereby extending the half-life of IgG in the body and maintaining albumin homeostasis.
• The genome of the mouse DR3 gene encoding the full-length protein was replaced with human DR3 counterpart in B-hDR3/hFcRn mice. The human full-length FCGRT cDNA was inserted into the Fcgrt exon 2 of wild-type mice.
• Mouse DR3 protein was exclusively detectable on T cells, CD4+ T cells and Treg cells from the spleen of wild-type C57BL/6JNifdc mice, and human DR3 protein was exclusively detectable on T cells, CD4+ T cells and Treg cells from the spleen of homozygous B-hDR3/hFcRn mice. Human FcRn protein was exclusively detectable in homozygous B-hDR3/hFcRn mice.
• Application: This product is used for pharmacodynamics and safety evaluation of  drugs.

Gene targeting strategy for B-hDR3/hFcRn mice. The exons 1-10 of mouse Tnfrsf25 gene that encode the whole molecule (ATG to STOP codon), including promoter and 5’UTR were replaced by human counterparts in B-hDR3/hFcRn mice. The 3’UTR region of the mouse gene are retained. The human TNFRSF25 expression is driven by human TNFRSF25 promoter, while mouse Tnfrsf25 gene transcription and translation will be disrupted.

The human full-length FCGRT cDNA was inserted into the Fcgrt exon 2 of wild-type mice.

Strain specific TNFRSF25 expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hDR3/hFcRn mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hDR3/hFcRn mice (H/H;H/H) stimulated with anti-mouse CD3ε antibody and anti-mouse CD28 antibody in vivo for 24 h, protein expression was analyzed with anti-mouse DR3 antibody (Biolegend, 144407) and anti-human DR3 antibody (Biolegend, 307105) by flow cytometry. Mouse DR3 was detectable in T cells of wild-type C57BL/6JNifdc mice, human DR3 was detectable in T cells of homozygous B-hDR3/hFcRn mice.

Strain specific TNFRSF25 expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hDR3/hFcRn mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hDR3/hFcRn mice (H/H;H/H) stimulated with anti-mouse CD3ε antibody and anti-mouse CD28 antibody in vivo for 24 h, protein expression was analyzed with anti-mouse DR3 antibody (Biolegend, 144407) and anti-human DR3 antibody (Biolegend, 307105) by flow cytometry. Mouse DR3 was detectable in CD4+ T cells of wild-type C57BL/6JNifdc mice, human DR3 was detectable in CD4+ T cells of homozygous B-hDR3/hFcRn mice.

Strain specific TNFRSF25 expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hDR3/hFcRn mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hDR3/hFcRn mice (H/H;H/H) stimulated with anti-mouse CD3ε antibody and anti-mouse CD28 antibody in vivo for 24 h, protein expression was analyzed with anti-mouse DR3 antibody (Biolegend, 144407) and anti-human DR3 antibody (Biolegend, 307105) by flow cytometry. Mouse DR3 was detectable in Treg cells of wild-type C57BL/6JNifdc mice, human DR3 was detectable in Treg cells of homozygous B-hDR3/hFcRn mice.

Western blot analysis of FcRn protein expression in homozygous B-hDR3/hFcRn mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hDR3/hFcRn mice (H/H;H/H), and then analyzed by western blot with species-specific anti-FcRn antibody (Novus Biologicals, NBP1-89128). 40 μg total proteins were loaded for western blotting analysis. Human FcRn was detected in heart, liver, spleen, lung, kidney and colon from homozygous B-hDR3/hFcRn mice.