• C-type lectin member 5A (CLEC5A), also known as myeloid DAP12-associating lectin (MDL-1), is a pattern recognition receptor which plays a role in innate immune system. It is a type II transmembrane protein that is expressed by monocytes, macrophages and neutrophils. It requires association with an adaptor protein, DAP12 or DAP10, activation the Syk-AKT signaling pathways. CLEC5A participates in multiple acute and chronic inflammatory diseases, such as hemorrhagic fever, lethal shock, and the development of autoimmune arthritis. Some recent studies suggest that activating CLEC5A can enhance the phagocytosis of macrophages, demonstrating anti-tumor activity
• The exons 3-7 of mouse Clec5a gene that encode the extracellular domain are replaced by human counterpart gene sequences in B-hCLEC5A mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The human CLEC5A expression is driven by endogenous mouse Clec5a promoter, while mouse Clec5a gene transcription and translation will be disrupted.
• Mouse CLEC5A was detectable in wild-type mice. Human CLEC5A was detectable in homozygous B-hCLEC5A mice.
• The mice can be used for preclinical studies of target-related disease especially in pharmacodynamics and safety evaluations.

Gene targeting strategy for B-hCLEC5A mice. The exons 3-7 of mouse Clec5a gene that encode the extracellular domain are replaced by human counterpart gene sequences in B-hCLEC5A mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The human CLEC5A expression is driven by endogenous mouse Clec5a promoter, while mouse Clec5a gene transcription and translation will be disrupted.

Strain specific CLEC5A expression analysis in homozygous B-hCLEC5A mice by flow cytometry. Bone marrow was collected from wild-type C57BL/6JNifdc (+/+) and homozygous B-hCLEC5A mice (H/H), and analyzed by flow cytometry with anti-mouse CLEC5A antibody (R&D, FAB1639P) and anti-human CLEC5A antibody (R&D, FAB2384A). mCLEC5A was detectable in wild-type and homozygous mice. hCLEC5A was only detectable in homozygous B-hCLEC5A mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific analysis of CLEC5A mRNA expression in wild-type C57BL/6JNifdc mice and homozygous B-hCLEC5A mice by RT-PCR. Myeloid cells RNA was isolated from wildtype C57BL/6JNifdc mice (+/+) and homozygous B-hCLEC5A mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human CLEC5A primers. Mouse Clec5a mRNA were detectable in wild-type mice. Human CLEC5A mRNA was detectable only in homozygous B-hCLEC5A mice but not in wild-type mice.