hCLDN18.2 Mouse
Product Name
hCLDN18.2 Mouse
Product ID
I001020
Strain Name
C57BL/6NCya-Cldn18em1(hCLDN18)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “hCLDN18.2 Mouse (Catalog I001020) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CLDN18
Gene Alias
SFTA5, SFTPJ
NCBI ID
Chromosome
Chr 3 (Human)
MGI ID
Datasheet
Strain Description
The Claudins (CLDNs) protein family is a type of integrin membrane protein found in the tight junctions of epithelial and endothelial cells. Its structure includes four transmembrane domains and two extracellular loops, making it a transmembrane protein located on the cell membrane surface. To date, 24 human Claudins genes have been discovered, with family members showing high consistency, particularly in the transmembrane domains. CLDNs are closely related to the maintenance of osmotic pressure, barrier function, and cell polarity in epithelial cells [1]. In addition, the expression of CLDNs changes significantly during the development of many tumors, and numerous studies on tumor treatment specifically targeting CLDNs have been conducted.
The human CLDN18 gene has two optional first exons, producing two different protein isoforms, CLDN18.1 and CLDN18.2, which differ by only eight amino acids in the first extracellular domain [2]. CLDN18.1 is mainly expressed in lung tissue, while CLDN18.2 shows specificity in the digestive tract. In normal tissues, the expression of CLDN18.2 is low, but it is abnormally high during the development of various malignant tumors in the digestive system. Especially in gastric cancer tissues, the expression of CLDN18.2 is consistently and stably high. In addition, abnormal activation and overexpression of CLDN18.2 have been observed in malignant tumors such as colon cancer, liver cancer, head and neck cancer, bronchial cancer, and non-small cell lung cancer [3].
This strain is a humanized mouse model of the Cldn18 gene. Through gene editing technology, the mouse Cldn18 gene is replaced with the human CLDN18.2 gene CDS sequence, while retaining the 3’UTR region of the mouse Cldn18 gene. Homozygous hCLDN18.2 mice are viable and fertile and can be used for the development and validation of CLDN18.2-targeted drugs and the study of the mechanism of gastrointestinal tumors.
Reference
Günzel D. Claudins: vital partners in transcellular and paracellular transport coupling. Pflugers Arch. 2017 Jan;469(1):35-44.
Niimi T, Nagashima K, Ward JM, Minoo P, Zimonjic DB, Popescu NC, Kimura S. claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing. Mol Cell Biol. 2001 Nov;21(21):7380-90.
Kumar V, Soni P, Garg M, Kamholz S, Chandra AB. Emerging Therapies in the Management of Advanced-Stage Gastric Cancer. Front Pharmacol. 2018 Sep 13;9:404.
Strain Strategy
The mouse Cldn18 gene was replaced with the gene expression component “Human CLDN18 CDS-3’UTR of mouse Cldn18”.
Figure 1. Gene editing strategy for hCLDN18.2 mice.
Application Area
Development and screening of CLDN18.2 targeted drugs;
Evaluation of the efficacy and safety of CLDN18.2 targeted drugs;
Research on malignant tumors of the digestive tract.
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