• The KLKB1 gene encodes a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation, and inflammation. Plasma prekallikrein (PPK) is a glycoprotein predominantly synthesized in the liver. This protein is synthesized in the liver and circulates in the bloodstream. Factor XII converts prekallikrein into another protein called plasma kallikrein, which in turn helps activate additional factor XII.
• Gene targeting strategy for B-hKLKB1 mice. The exons 2-15 of mouse Klkb1 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hKLKB1 mice. The promoter and 5’UTR region of the mouse gene were retained. The human KLKB1 expression was driven by endogenous mouse Klkb1 promoter, while mouse Klkb1 gene transcription and translation was disrupted.
• Human Prekallikrein was exclusively detectable in heterozygous B-hKLKB1 mice (H/+) but not in wild-type mice.
• Application: This product is used for pharmacodynamics and safety evaluation of Hereditary angioedema (HAE).

Gene targeting strategy for B-hKLKB1 mice. The exons 2-15 of mouse Klkb1 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hKLKB1 mice. The promoter and 5’UTR region of the mouse gene were retained. The human KLKB1 expression was driven by endogenous mouse Klkb1 promoter, while mouse Klkb1 gene transcription and translation was disrupted.

Strain specific KLKB1 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hKLKB1 mice by ELISA. Plasma was collected from wild-type C57BL/6JNifdc mice (+/+) (male, n=3, 6-week-old) and homozygous B-hKLKB1 mice (H/H) (male, n=2, 6-week-old; female, n=3, 6-week-old). Expression level of human KLKB1 was analyzed by ELISA (Human Prekallikrein 1B ELISA Kit, Abcam, ab202405). Human KLKB1 was exclusively detectable in homozygous B-hKLKB1 mice (male, n=2, 6-week-old; female, n=3, 6-week-old). Values are expressed as mean ± SEM.

The inhibitory efficiency of the nucleic acid drugs against human KLKB1 in heterozygous B-hKLKB1 mice. Heterozygous B-hKLKB1 mice (H/+) were randomly divided into two groups (G1: n=3, 8 weeks old, female; G2: n=3, 8 weeks old, female). The human KLKB1 targeted nucleic acid drug (from a client) and saline were administered to the mice individually. The mice were sacrificed on day 7. (A) The schematic diagram of experimental processing. (B) The changes in KLKB1 protein expression levels in serum on day 7 after administration, compared to the levels before administration. The human KLKB1 in the treatment group (G2) was significantly reduced compared to the control group on day 7 after administration. Values are expressed as mean ± SEM.