CLDN6 (claudin 6, gene ID 9074) encodes a transmembrane protein forming the backbone of epithelial cell tight junctions, which is adjacent to another family member CLDN9 on chromosome 16, belongs to the claudin family. CLDN6 is expressed by epithelial cells where it participates in tissue development and the maintenance of tight junction integrity. The expression of CLDN6 in non-cancerous tissue is restricted to early stages of development, as in healthy adult tissues it is transcriptionally silenced. A fact which has led to consideration of CLDN6 as circulating marker for pregnancy. The protein is one of the entry cofactors for hepatitis C virus. The methylation of this gene may be involved in esophageal tumorigenesis. In various cancer types such as ovarian, lung, gastric, breast and pediatric cancers CLDN6 expression is aberrantly activated. Studies have shown that CLDN6 is associated with the proliferation migration and apoptosis of tumor cells and help to regulate defense and barrier functions, as well as differentiation and polarity in epithelial and endothelial cells.
(A) CLDN6 promotes tumor progression in gastric cancer.
(B) The EC2-dependent trans-interaction of CLDN6 recruits and activates SFKs resulting in stimulating the downstream PI3K/AKT pathway. This CLDN6 adhesion signal phosphorylates the downstream signaling.
(C) High CLDN6 expression enhanced the proliferative and invasive abilities of tumors in vivo
Gene targeting strategy for B-hCLDN6 mice
The full encoding sequence region of mouse CLDN6 gene was replaced by the counterpart gene sequence of human CLDN6 in B-hCLDN6 mice.
Protein expression analysis
Strain specific CLDN6 expression analysis in heterozygous B-hCLDN6 mice by western blot. Liver tissue was collected from wild-type C57BL/6 (+/+) and heterozygous B-hCLDN6 mice (H/+) and analyzed by western blotting with species-specific anti-CLDN6 antibody. Mouse CLDN6 was detectable in wild-type mice and heterozygous B-hCLDN6 mice. Human CLDN6 was exclusively detectable in heterozygous B-hCLDN6 mice but not in wild-type mice.
Strain specific CLDN6 expression analysis in homozygous B-hCLDN6 mice by western blot. Liver tissue and thymus were collected from wild-type C57BL/6 (+/+) and homozygous B-hCLDN6 mice (H/H) and analyzed by western blotting with species-specific anti-CLDN6 antibody. Mouse CLDN6 was detectable in wild-type mice. Human CLDN6 was exclusively detectable in homozygous B-hCLDN6 mice but not in wild-type mice.