• ALK7 serves as a receptor for specific ligands within the TGF-β superfamily, such as Activin E, Activin B, and GDF-3. This receptor demonstrates high expression levels in both rodent and human adipose tissue. Through inhibition of ALK7 in adult mice has been shown to inhibit diet-induced weight gain, reduce fat accumulation and adipocyte size, and enhance adipocyte lipolysis alongside β-adrenergic signaling activity (DOI: 10.7554/eLife.03245).
• The part of exon 2 to exon 9 of mouse Acvr1c gene that encode the whole molecule including 3’UTR, are replaced by P2A, human full coding sequence (CDS) and human 3’UTR in B-hALK7 mice. The promoter and 5’UTR region of the mouse gene are retained. The human ACVR1C expression is driven by the endogenous mouse Acvr1c promoter, while mouse Acvr1c gene transcription and translation will be disrupted.
• The mice can be used for preclinical pharmacodynamics studies of target-related diseases

Gene targeting strategy for B-hALK7 mice. The part of exon 2 to exon 9 of mouse Acvr1c gene that encode the whole molecule including 3’UTR, are replaced by human full coding sequence (CDS) and human 3’UTR in B-hALK7 mice. The promoter and 5’UTR region of the mouse gene are retained. The human ACVR1C expression is driven by the endogenous mouse Acvr1c promoter, while mouse Acvr1c gene transcription and translation will be disrupted.

Strain specific analysis of ALK7 mRNA expression in wild-type C57BL/6JNifdc mice and B-hALK7 mice by RT-PCR. Perirenal fat RNA was isolated from wild-type C57BL/6JNifdc mice (+/+) and heterozygous B-hALK7 mice (H/+), then cDNA libraries were synthesized by reverse transcription, followed by RT-qPCR with human ALK7 primers. Human ALK7 mRNA was exclusively detectable in B-hALK7 mice but not in wild-type mice.

Strain specific analysis of ALK7 mRNA expression in wild-type C57BL/6JNifdc mice and B-hALK7 miceby RT-qPCR. Perirenal fat, Perigonadal fat, and Brown fat RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and heterozygous B-hALK7 mice (H/+), then cDNA libraries were synthesized by reverse transcription, followed by RT-qPCR with mouse or human ALK7 primers. Human ALK7 mRNA was exclusively detectable in B-hALK7 mice but not in wild-type mice.