• Background: The protein encoded by SPARC is a matricellular protein with anti-proliferative and anti-adhesive properties, which regulates the interaction between cells and the surrounding extracellular matrix. This protein is overexpressed in conditions such as injury, regeneration, obesity, cancer, and inflammation, making it a potential therapeutic target for diseases like cancer and inflammation.
• Targeting strategy: The exons 1-10 of mouse SPARC gene that encode the whole molecule (ATG to STOP codon), including 5’UTR and 3’UTR are replaced by human counterparts in B-hSPARC mice. The human SPARC expression is driven by human SPARC promoter, while mouse Sparc gene transcription and translation will be disrupted.
• Validation: Human SPARC protein was detectable in the B-hSPARC mice but not in C57BL/6JNifdc mice.
• Application: Tumor cell lines inoculated in B-hSPARC mice can be used to study the in vivo efficacy and safety evaluation of antibody drugs

Gene targeting strategy for B-hSPARC mice. The exons 1-10 of mouse SPARC gene that encode the whole molecule (ATG to STOP codon), including 5’UTR and 3’UTR are replaced by human counterparts in B-hSPARC mice. The human SPARC expression is driven by human SPARC promoter, while mouse Sparc gene transcription and translation will be disrupted.

Strain specific SPARC expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hSPARC mice by ELISA. Serum was collected from wild-type C57BL/6JNifdc mice (+/+) (female, n=3, 7-week-old) and homozygous B-hSPARC mice (H/H) (female, n=3, 7-week-old). Expression level of human SPARC was analyzed by ELISA (anti-human SPARC ELISA kit: Abcam, ab220654). Human SPARC was exclusively detectable in homozygous B-hSPARC mice. Values are expressed as mean ± SEM. ND=Not Detected.