Description
- 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 rats Muc1 genome that encodes the full-length protein was replaced by human MUC1 genome in B-hMUC1 rats.
- MUC1 was detectable in the spleen, lung, kidney, brain, colon and small intestine of homozygous B-hMUC1 rats. There was no detectable expression of hMUC1 in various tissues of SD rats.
- B-hMUC1 rats can be used to study the in vivo safe evaluation of MUC1 antibody drugs.
Targeting strategy
Gene targeting strategy for B-hMUC1 rats. The rats Muc1 genome that encodes the full-length protein was replaced by human MUC1 genome in B-hMUC1 rats.
Protein expression profile of MUC1
Immunohistochemical (IHC) analysis of MUC1 protein expression in SD wild-type mice and B-hMUC1 rats. Nine major tissues were collected from SD rats and homozygous B-hMUC1 rats (female/male, 8-week-old), and analyzed by IHC with anti-MUC1 antibody (Abcam, ab245693). MUC1 was detectable in the spleen, lung, kidney, brain, colon and small intestine (D, E, G, H, I) of homozygous B-hMUC1 rats (Figure 2). There was no detectable expression of hMUC1 in various tissues of SD rats (Figure 1). A summary of the expression levels in various tissues of SD rats and B-hMUC1 rats is presented in Table 1.
mRNA expression analysis
Strain specific analysis of MUC1 mRNA expression in wild-type SD rats and B-hMUC1 rats by RT-PCR. Stomach RNA were isolated from wildtype SD rats (+/+) and homozygous B-hMUC1 rats (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with rats or human MUC1 primers. Rats Muc1 mRNA was detectable in wild-type SD rats. Human MUC1 mRNA was detectable only homozygous B-hMUC1 rats but not in wild-type SD rats.
* When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-hMUC1 rats] (Cat# 113106) was purchased from Biocytogen.