NKX2-3 (NK2 homeobox 3)

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URI: http://hdl.handle.net/2042/62506  |   DOI : https://doi.org/10.4267/2042/62506
Title: NKX2-3 (NK2 homeobox 3)
Author: Lin, Zhenwu; Hegarty, John P; Floros, Joanna; Franke, Andre
Abstract: NKX2-3 gene is a member of the homeobox, NKX family. The gene encodes a homeodomain-containing transcription factor. GO (gene ontology) annotations related to this gene include sequence-specific DNA binding and gene-specific transcription factor activity. NKX2-3 is essential for normal development and functions of the small intestine and spleen of embryonic and adult mice. Disruption of Nkx2-3 in mice results in postnatal lethality and abnormal development of the small intestine and the spleen. Villus formation in the small intestine appears considerably delayed in Nkx2-3(null) fetuses due to reduced proliferation of the epithelium, while massively increased growth of crypt cells follows in surviving adults. A complex intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggest deranged leukocyte homing. RT-PCR and immunohistochemistry revealed that NKX2-3 controls regional expression of leukocyte homing coreceptor mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in specialized endothelial cells of the viscera. This indicates a potential role for NXK2-3 in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion. Studies of disease association indicated that NKX2-3 is associated with IBD (both Crohn's disease and ulcerative colitis), intestinal fibrosis, colon rectal cancer, and dental caries.
Subject: NKX2-3; inflammatory bowel disease (IBD); Crohn's disease (CD); ulcerative disease (UC); homeodomain-containing transcription factor; Genes Section; Cell Survival; Down-Regulation; Endothelial Cells/*cytology/metabolism; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide/metabolism; MicroRNAs/*genetics/metabolism; *Neovascularization, Physiologic; *Oxidative Stress; PTEN Phosphohydrolase/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Up-Regulation; Humans; Inflammatory Bowel Diseases/*genetics/physiopathology/therapy; Adolescent; Adult; Aged; Alleles; Asian Continental Ancestry Group/genetics; Case-Control Studies; Chil
Publisher: Jean-Loup Huret (Editor-in-Chief)
Date: 2016

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