Description
- Human KLK5(Kallikrein Related Peptidase 5) 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.
- KLK6 (Kallikrein Related Peptidase 6) encodes a member of the kallikrein subfamily of the peptidase S1 family of serine proteases. Diseases associated with KLK6 include Breast Cyst and Papillary Carcinoma. Among its related pathways are Collagen chain trimerization and Vitamin D receptor pathway. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and peptidase activity. An important paralog of this gene is KLK13.
- KLK7 (Kallikrein Related Peptidase 7) , this gene encodes a member of the kallikrein subfamily of serine proteases. These enzymes have diverse physiological functions and many kallikrein genes are biomarkers for cancer. The encoded protein has chymotrypsin-like activity and plays a role in the proteolysis of intercellular cohesive structures that precedes desquamation, the shedding of the outermost layer of the epidermis. Diseases associated with KLK7 include Netherton Syndrome and Dermatitis. Among its related pathways are Collagen chain trimerization and Developmental Cell Lineages of the Integumentary System. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and serine-type peptidase activity. An important paralog of this gene is KLK5.
- The exons 1-6 of mouse Klk5 gene, the exons 1-7 of mouse Klk6 gene, exons 1-6 of mouse Klk7 gene, that encode the whole molecule were replaced by human counterparts in B-hKLK5/hKLK6/hKLK7 mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were replaced by human counterparts. The human KLK5, KLK6, KLK7 expression is driven by human KLK5, KLK6, KLK7 promoter, while mouse Klk5, Klk6, Klk7 gene transcription and translation will be disrupted.
- Human KLK5, KLK6, KLK7 were exclusively detectable in B-hKLK5/hKLK6/hKLK7 mice, but not in wild-type C57BL/6JNifdc mice.
- Application: This product is used for preclinical safety evaluation of antibody drugs.
Targeting strategy
Gene targeting strategy for B-hKLK5/hKLK6/hKLK7 mice. The exons 1-6 of mouse Klk5 gene, the exons 1-7 of mouse Klk6 gene, exons 1-6 of mouse Klk7 gene, that encode the whole molecule were replaced by human counterparts in B-hKLK5/hKLK6/hKLK7 mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were replaced by human counterparts. The human KLK5, KLK6, KLK7 expression is driven by human KLK5, KLK6, KLK7 promoter, while mouse Klk5, Klk6, Klk7 gene transcription and translation will be disrupted.
Protein expression analysis in ear
Strain specific KLK5, KLK6 and KLK7 expression analysis in wild-type C57BL/6JNifdc mice and heterozygous B-hKLK5/hKLK6/hKLK7 mice by ELISA. Ear was collected from wild-type C57BL/6JNifdc mice (+/+) (female, n=1, 6-week-old) and heterozygous B-hKLK5/hKLK6/hKLK7 mice (H/+) (female, n=1, 6-week-old) . Expression level of human KLK5, KLK6 and KLK7 were analyzed by ELISA (Human Kallikrein 5 Quantikine ELISA Kit: R&D, DKK500, Human Kallikrein 6 SimpleStep ELISA Kit, abcam, ab287163; Human Kallikrein 7 SimpleStep ELISA Kit, abcam, ab287175). Human KLK5, KLK6 and KLK7 were exclusively detectable in heterozygous B-hKLK5/hKLK6/hKLK7 mice but not in wild-type C57BL/6JNifdc mice.
* When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-hKLK5/hKLK6/hKLK7 mice] (Cat# 114038) was purchased from Biocytogen.
