B6-hMADCAM1 Mouse
Product Name
B6-hMADCAM1 Mouse
Product ID
C001816
Strain Name
C57BL/6NCya-Madcam1tm1(hMADCAM1)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hMADCAM1 Mouse (Catalog C001816) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
MADCAM1
Gene Alias
MACAM1
NCBI ID
Chromosome
Chr 19 (Human)
MGI ID
Datasheet
Strain Description
The MADCAM1 gene encodes Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an endothelial cell adhesion molecule crucial for guiding leukocyte traffic. MAdCAM-1 is preferentially expressed on endothelial cells of gut-associated lymphoid tissues (GALT), such as Peyer's patches and mesenteric lymph nodes, and venules of the intestinal lamina propria [1]. Its expression is inducible by pro-inflammatory cytokines like TNF-α, and also influenced by cell-cell interactions and cellular density. The encoded protein is a member of the immunoglobulin superfamily, featuring two Ig-like domains, a mucin-like region, a transmembrane domain, and a cytoplasmic tail. MAdCAM-1 primarily functions by interacting with leukocyte α4β7 integrin (LPAM-1), L-selectin, and VLA-4 (α4β1) on myeloid cells, directing these immune cells into mucosal and inflamed tissues, playing a vital role in gut immune surveillance and lymphocyte homing [2]. Aberrant or upregulated MAdCAM-1 expression is strongly associated with various inflammatory diseases, particularly inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis, where its overexpression contributes to excessive lymphocyte accumulation and inflammation in the gut [3]. It is also implicated in other conditions such as primary sclerosing cholangitis, type 1 diabetes, and certain cancers where gut inflammation or lymphocyte trafficking is key [2-4].
The B6-hMADCAM1 mouse is a humanized model, constructed by replacing the sequences from exon 1 to a partial intron 4 of mouse Madcam1 with the sequences from the ATG start codon to the TGA stop codon of the human MADCAM1 gene, and the 3' UTR of mouse Madcam1-rBG pA cassette is inserted downstream of the TGA stop codon. B6-hMADCAM1 mice can be used for research into the pathogenesis of inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis, primary sclerosing cholangitis, type 1 diabetes, and certain cancers. They are also useful for the screening, development, and safety evaluation of MADCAM1-targeted drugs.
Reference
Kuhbandner K, Hammer A, Haase S, Terbrack E, Hoffmann A, Schippers A, Wagner N, Hussain RZ, Miller-Little WA, Koh AY, Stoolman JS, Segal BM, Linker RA, Stüve O. MAdCAM-1-Mediated Intestinal Lymphocyte Homing Is Critical for the Development of Active Experimental Autoimmune Encephalomyelitis. Front Immunol. 2019 Apr 26;10:903.
He R, Zhao S, Cui M, Chen Y, Ma J, Li J, Wang X. Cutaneous manifestations of inflammatory bowel disease: basic characteristics, therapy, and potential pathophysiological associations. Front Immunol. 2023 Oct 26;14:1234535.
Ozawa N, Yokobori T, Osone K, Bilguun EO, Okami H, Shimoda Y, Shiraishi T, Okada T, Sano A, Sakai M, Sohda M, Miyazaki T, Ide M, Ogawa H, Yao T, Oyama T, Shirabe K, Saeki H. MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals. Int J Cancer. 2024 Jan 15;154(2):359-371.
Li Y, Gunderson RC, Xu Z, Ai W, Shen F, Ye J, Xu B, Michie SA. Mucosal Addressin Cell Adhesion Molecule-1 Mediates T Cell Migration into Pancreas-Draining Lymph Nodes for Initiation of the Autoimmune Response in Type 1 Diabetes. Int J Mol Sci. 2024 Oct 22;25(21):11350.
Strain Strategy
The coding sequence of exon 1 to partial intron 4 sequences will be replaced with the sequences from the ATG start codon to the TGA stop codon of the human MADCAM1 gene, and the 3' UTR of mouse Madcam1-rBG pA cassette will be inserted downstream of the TGA stop codon.
Figure 1. Gene editing strategy of B6-hMADCAM1 Mice.
Application Area
MADCAM1-targeted drug screening, development, and evaluation;
Research on the pathological mechanisms and therapeutic approaches of inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis;
Research on the primary sclerosing cholangitis;
Research on type 1 diabetes;
Research on certain cancers.
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