• Background: activin A receptor type 1B (ACVR1B) is an important Type I receptor in the TGF-β superfamily, typically functioning as a tumor suppressor. Its frequent inactivation in various cancers makes it a highly potential therapeutic target. Current research is focused on developing novel drugs that can specifically reactivate this pathway, offering a new treatment paradigm for cancer patients..
• Targeting strategy: The exons 2-3 of mouse Acvr1b gene that encode extracellular domain are replaced by human counterparts in B-hACVR1B mice. The genomic region of mouse Acvr1b gene that encodes transmembrane domain and cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric ACVR1B expression is driven by endogenous mouse Acvr1b promoter, while mouse Acvr1b gene transcription and translation will be disrupted.
• Validation: Human ACVR1B mRNA and protein were detected in the B-hACVR1B mice but not in C57BL/6JNifdc mice.
• Application: Tumor cell lines inoculated in B-hACVR1B mice can be used to study the in vivo efficacy and safety evaluation of antibody drugs.

Gene targeting strategy for B-hACVR1B mice. The exons 2-3 of mouse Acvr1b gene that encode extracellular domain are replaced by human counterparts in B-hACVR1B mice. The genomic region of mouse Acvr1b gene that encodes transmembrane domain and cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric ACVR1B expression is driven by endogenous mouse Acvr1b promoter, while mouse Acvr1b gene transcription and translation will be disrupted.

Western blot analysis of ACVR1B protein expression in wild-type C57BL/6JNifdc mice and homozygous B-hACVR1B mice. Various tissue lysates were collected from C57BL/6JNifdc (+/+) and homozygous B-hACVR1B mice (H/H), and then analyzed by western blot with anti-ACVR1B antibody (abcam, ab317379). 40 μg total proteins were loaded for western blotting analysis. ACVR1B was detectable in C57BL/6JNifdc (+/+) and B-hACVR1B mice (H/H). The antibody was cross-reactive between human and mouse.

Strain specific analysis of ACVR1B mRNA expression in wild-type C57BL/6JNifdc mice and B-hACVR1B mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hACVR1B mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human ACVR1B primers. mouse Acvr1b mRNA was only detectable in wild-type mice. Human ACVR1B mRNA was exclusively detectable in homozygous B-hACVR1B mice but not in wild-type mice.