RGD Reference Report - Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera. - Rat Genome Database

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Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera.

Authors: Wang, CC  Biben, C  Robb, L  Nassir, F  Barnett, L  Davidson, NO  Koentgen, F  Tarlinton, D  Harvey, RP 
Citation: Wang CC, etal., Dev Biol 2000 Aug 15;224(2):152-67.
RGD ID: 1549651
Pubmed: PMID:10926756   (View Abstract at PubMed)
DOI: DOI:10.1006/dbio.2000.9749   (Journal Full-text)

Regulated emigration of blood-borne leukocytes plays a defining role in lymphoid organ development, immune surveillance, and inflammatory responses. We report here that mice deficient in the homeobox gene Nkx2-3, expressed in developing visceral mesoderm, show a complex intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged leukocyte homing. Mutant Peyer's patches were reduced in number and size, intestinal villi contained few IgA(+) plasma cells, and mutant spleens were small and often atrophic, showing fused periarterial lymphoid sheaths, partially merged T and B cell zones, an absent marginal zone, and a dearth of macrophages in red pulp. Semiquantitative RT-PCR analysis and immunohistochemistry revealed down-regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in endothelial cells in which Nkx2-3 is normally expressed. MAdCAM-1 is a member of the immunoglobulin superfamily, acting as an endothelial cell ligand for leukocyte homing receptors L-selectin and alpha4beta7 integrin. Our data suggest a role for a homeodomain factor in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3.

Objects referenced in this article
Gene Adgre1 adhesion G protein-coupled receptor E1 Mus musculus
Gene Apoa4 apolipoprotein A-IV Mus musculus
Gene Apobec1 apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 Mus musculus
Gene Btc betacellulin, epidermal growth factor family member Mus musculus
Gene Cd34 CD34 antigen Mus musculus
Gene Cdx1 caudal type homeobox 1 Mus musculus
Gene Cdx2 caudal type homeobox 2 Mus musculus
Gene Cnn1 calponin 1 Mus musculus
Gene Cxcl13 C-X-C motif chemokine ligand 13 Mus musculus
Gene Efnb2 ephrin B2 Mus musculus
Gene Gata5 GATA binding protein 5 Mus musculus
Gene Gata6 GATA binding protein 6 Mus musculus
Gene Glycam1 glycosylation dependent cell adhesion molecule 1 Mus musculus
Gene Hand1 heart and neural crest derivatives expressed 1 Mus musculus
Gene Hbegf heparin-binding EGF-like growth factor Mus musculus
Gene Hlx H2.0-like homeobox Mus musculus
Gene Icam2 intercellular adhesion molecule 2 Mus musculus
Gene Lct lactase Mus musculus
Gene Ltbr lymphotoxin B receptor Mus musculus
Gene Madcam1 mucosal vascular addressin cell adhesion molecule 1 Mus musculus
Gene Mef2b myocyte enhancer factor 2B Mus musculus
Gene Nkx2-3 NK2 homeobox 3 Mus musculus
Gene Slc40a1 solute carrier family 40 (iron-regulated transporter), member 1 Mus musculus
Gene Tagln transgelin Mus musculus

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