• The IL10RA gene encodes the alpha subunit of the interleukin-10 receptor, a key mediator of IL-10–dependent anti-inflammatory signaling and immune tolerance. Defects in IL10RA are associated with very-early-onset colitis and immune regulatory disorders. The IL2RG gene encodes the common gamma chain, an essential component shared by the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. It is indispensable for the development and function of T cells, B cells, and NK cells, and mutations in IL2RG are the primary cause of X-linked severe combined immunodeficiency (X-SCID).
• The exons 1-5 and part of exon 6 of mouse Il10ra gene that encode signal peptide, extracellular domain, transmembrane domain, and part of cytoplasmic region are replaced by human counterparts in B-hIL10RA/hIL2RG mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are retained. The human IL10RA expression is driven by endogenous mouse Il10ra promoter, while mouse Il10ra gene transcription and translation will be disrupted. The exons 1-8 of mouse Il2rg gene that encode the whole molecule (ATG to STOP codon) are replaced by human counterparts in B-hIL10RA/hIL2RG mice. The promoter, 3’UTR and 5’UTR region of the mouse gene are retained. The human IL2RG expression is driven by endogenous mouse Il2rg promoter, while mouse Il2rg gene transcription and translation will be disrupted.
• B-hIL10RA/hIL2RG mice were derived from mating B-hIL10RA mice(110083) and B-hIL2RG mice(110087). Human IL10RA was detectable in peritoneal macrophages of B-hIL10RA/hIL2RG mice. Human IL2RG was detectable on T cells and NK cells from spleen of B-hIL10RA/hIL2RG mice.

Gene targeting strategy for B-hIL10RA/hIL2RG mice. The exons 1-5 and part of exon 6 of mouse Il10ra gene that encode signal peptide, extracellular domain, transmembrane domain, and part of cytoplasmic region are replaced by human counterparts in B-hIL10RA/hIL2RG mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are retained. The human IL10RA expression is driven by endogenous mouse Il10ra promoter, while mouse Il10ra gene transcription and translation will be disrupted.

The exons 1-8 of mouse Il2rg gene that encode the whole molecule (ATG to STOP codon) are replaced by human counterparts in B-hIL10RA/hIL2RG mice. The promoter,3’UTR and 5’UTR region of the mouse gene are retained. The human IL2RG expression is driven by endogenous mouse Il2rg promoter, while mouse Il2rg gene transcription and translation will be disrupted.

IL10RA expression analysis in wild-type mice and homozygous humanized B-hIL10RA/hIL2RG mice by flow cytometry. Peritoneal macrophages were collected from C57BL/6JNifdc mice (+/+) (Female, 6-week-old, n=1) and B-hIL10RA/hIL2RG mice (H/H) (Female, 6-week-old, n=1). Protein expression was analyzed with anti-IL10RA antibody (Biolegend, 308811; Biolegend, 112705) by flow cytometry. Human IL10RA was detected in homozygous B-hIL10RA/hIL2RG mice.

IL10RA expression analysis in wild-type mice and homozygous humanized B-hIL10RA/hIL2RG mice by flow cytometry. Peritoneal macrophages were collected from C57BL/6JNifdc mice (+/+) (Female, 6-week-old, n=1) and B-hIL10RA/hIL2RG mice (H/H) (Female, 6-week-old, n=1). Protein expression was analyzed with anti-IL10RA antibody (Biolegend, 308811; Biolegend, 112705) by flow cytometry. Human IL10RA was detected in homozygous B-hIL10RA/hIL2RG mice.

IL2RG expression analysis in wild-type mice and homozygous B-hIL10RA/hIL2RG mice by flow cytometry. Spleen T cells and NK cells were collected from C57BL/6JNifdc mice (+/+) (Female, 9-week-old, n=2; Male, 9-week-old, n=2) and B-hIL10RA/hIL2RG mice (H/H) (Female, 9-week-old, n=2; Male, 9-week-old, n=2). Protein expression was analyzed with anti-IL2RG antibody (Biolegend, 132308; Biolegend, 338606) by flow cytometry. Human IL2RG was detected in homozygous B-hIL10RA/hIL2RG mice.