• MUC1 (mucin 1) is a transmembrane glycoprotein (also known as CD227 or EMA) that protects the epithelial mucosal barrier. It is aberrantly overexpressed in various cancers (e.g., breast cancer, pancreatic cancer) and promotes tumor progression.
• MUC1 is a large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic cell lineages. MUC1 is a transmembrane glycoprotein with a large mucin-like extracellular domain that matures through several intermediate forms generated by proteolysis, and sequential addition and processing of numerous O-linked glycans that are heavily sialylated. MUC1 is highly polymorphic and each allele encodes a product that contains a different number of repeats (between 30 and 90) leading to large differences in molecular weight of the protein. 
• Its ​​sufficient oncogenicity​​ and ​​cell surface localization​​ make it a critical ​​therapeutic target for tumors​​. Targeted therapies, including antibodies (ADCs included), CAR-T, vaccines (e.g., targeting VNTR regions), and small-molecule inhibitors, are under ​​active R&D​​, with several having progressed to clinical trials.
• The mouse Muc1 genome that encodes the full-length protein was replaced by human MUC1 genome in B-NDG hMUC1 mice.
• MUC1 was detected in lung, brain, kidney, stomach, colon and skin in from wild-type B-NDG mice and homozygous B-NDG hMUC1 mice, the antibody was cross-reactive between human and mouse.
• Mouse Muc1 mRNA was detectable in wild-type mice. Human MUC1 mRNA was detectable only homozygous B-NDG hMUC1 mice but not in wild-type mice.
• B-hMUC1 mice can be used to study the in vivo efficacy evaluation of MUC1 antibody drugs.

Gene targeting strategy for B-NDG hMUC1 mice. The mouse Muc1 genome that encodes the full-length protein was replaced by human MUC1 genome in B-NDG hMUC1 mice.

Western blot analysis of MUC1 protein expression in homozygous B-NDG hMUC1 mice. Various tissue lysates were collected from wild-type B-NDG mice (+/+) and homozygous B-NDG hMUC1 mice (H/H), and then analyzed by western blot with anti-MUC1 antibody (Abcam, ab45167; Invitrogen, PA5-116457). 40 μg total proteins were loaded for western blotting analysis. MUC1 was detected in lung, brain, kidney, stomach, colon and skin in from wild-type B-NDG mice and homozygous B-NDG hMUC1 mice, the antibody was cross-reactive between human and mouse.

Strain specific analysis of MUC1 mRNA expression in wild-type B-NDG mice and B-NDG hMUC1 mice by RT-PCR. Stomach RNA were isolated from wildtype B-NDG mice (+/+) and homozygous B-NDG hMUC1 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human MUC1 primers. Mouse Muc1 mRNA was detectable in wild-type mice. Human MUC1 mRNA was detectable only homozygous B-NDG hMUC1 mice but not in wild-type mice.