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Role of the Kaiso gene in the development of inflammation in Mucin-2 defcient mice

https://doi.org/10.18699/VJ18.453

Abstract

The number of people with inflammatory bowel disease (IBD) is constantly increasing worldwide. The main factors that have effects on the etiology of the disease are genetic, environmental and immunological. However, the mechanism of disease development and effective treatment of IBD have not yet been found. Animal models help address these problems. The most popular model is considered to be transgenic models in which individual genes are knocked out. One of such models for the study of IBD are mice with a null mutation of the Muc2 gene encoding the Mucin-2 protein, which is involved in the formation of a protective mucin layer in the small and large intestine. Some of transcription factors that change the expression of intestinal genes are involved in the development of IBD and colorectal cancer. One of such transcription factors is “zinc fnger” domain-containing protein Kaiso which is able to bind to methylated DNA. In this study, we assessed the role of Kaiso in the development of intestinal inflammation using the experimental model of C57BL/6Muc2-/-Kaiso-/-. We have shown that mice with impaired intestinal barrier function that develop processes similar to human IBD also develop inflammatory responses, such as increased expression of Il1, Tnf and Il17a genes. The defciency of the Kaiso transcription factor in Mucin-2 knockout mice causes a decrease in the expression level of only the Cox2 and T3 genes. Perhaps a decline in the expression of the gene encoding cyclooxygenase-2 can lead to a decrease in the expression of the antibacterial factor Trefoil factor 3. However, in the experimental model of IBD, Kaiso protein did not play a signifcant role in the regulation of pro-inflammatory cytokines of tumor necrosis factor and interleukins 1 and 17.

About the Authors

E. A. Litvinova
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


K. M. Achasova
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


M. A. Borisova
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


S. V. Zhenilo
Federal Research Centre “Fundamentals of Biotechnology”, RAS, Institute of Bioengineering
Russian Federation
Moscow


E. B. Prokhortchouk
Federal Research Centre “Fundamentals of Biotechnology”, RAS, Institute of Bioengineering
Russian Federation
Moscow


E. N. Kozhevnikova
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


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