• Human KLK5 possesses a 29-amino acid signal peptide, a 37-amino acid activation peptide, and 237 amino acids containing the mature enzyme. KLK5 was initially identified in the normal human epidermis as the stratum corneum tryptic enzyme, where it takes part in the degradation of corneodesmosomes in the most external layer of human skin, giving as a result skin desquamation.
• IL‑4 and IL‑13 are shared IL‑4 receptor subunit alpha (IL‑4Rα), as a result, have some overlapping functions. The type I receptor, comprising IL‑4Rα and common cytokine receptor γ-chain (γc), only binds IL‑4. The type II receptor complex, comprising IL‑4Rα and IL‑13Rα1, is the primary receptor for IL‑13 but also binds IL‑4.
• The exons 1-5 of mouse Klk5 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hKLK5/hIL4/hIL4RA/hIL13 mice.
• The mouse Il4 gene that encodes the full length coding sequence was replaced by human IL4 counterpart gene sequences in B-hKLK5/hIL4/hIL4RA/hIL13 mice.
• The mouse Il4ra gene that encodes the extracellular region coding sequences was replaced by human IL4RA counterpart gene sequences in B-hKLK5/hIL4/hIL4RA/hIL13 mice.
• The mouse Il13 gene that encodes the full length coding sequence was replaced by human IL13 counterpart gene sequences in B-hKLK5/hIL4/hIL4RA/hIL13 mice.
• Human KLK5 was exclusively detectable in heterozygous B-hKLK5/hIL4/hIL4RA/hIL13 mice, but not in wild-type mice.
• Application: This product is used for pharmacodynamics and safety evaluation of  drugs.

Gene targeting strategy for B-hKLK5/hIL4/hIL4RA/hIL13 mice.

• The exons 1-5 of mouse Klk5 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hKLK5/hIL4/hIL4RA/hIL13 mice. The promoter, 5’UTR region of the mouse gene are retained. The KLK5 expression is driven by endogenous mouse Klk5 promoter, while mouse Klk5 gene transcription and translation will be disrupted.
• The exons 1-4 of mouse Il4 gene that encode the full length coding sequence were replaced by human IL4 exons 1-4 in B-hKLK5/hIL4/hIL4RA/hIL13 mice.
• The exons 4-7 of mouse Il4ra gene that encode the extracellular region coding sequences were replaced by human IL4RA exons 4-7 in B-hKLK5/hIL4/hIL4RA/hIL13 mice.
• The exons 1-4 of mouse Il13 gene that encode the full length coding sequence were replaced by human IL13 exons 1-4 in B-hKLK5/hIL4/hIL4RA/hIL13 mice.

Strain specific KLK5 expression analysis in wild-type C57BL/6JNifdc mice and humanized heterozygous B-hKLK5/hIL4/hIL4RA/hIL13 mice by ELISA. Ear was collected from wild-type C57BL/6JNifdc mice (+/+) (male, n=1, 9-week-old) and heterozygous B-hKLK5/hIL4/hIL4RA/hIL13 mice (H/+; H/H; H/H; H/H)  (male, n=1, 9-week-old). Expression level of human KLK5 was analyzed by ELISA (Human Kallikrein 5 Quantikine ELISA Kit: R&D, DKK500). Human KLK5 was exclusively detectable in B-hKLK5/hIL4/hIL4RA/hIL13 mice , but not in wild-type C57BL/6JNifdc mice. ND: not detectable.