Disease relevance of Sox18

• Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema [1].
• Lipopolysaccharide (LPS) extracted from three strains of Salmonella typhimurium, i.e., the rough Re mutant SL1102, the rough Ra mutant TV119, and the smooth strain SH4809, was first electrodialyzed (eLPS) and then divalent cation deprived by EDTA treatment and finally made monomeric by deoxycholate solubilization [2].
• In contrast, a high inoculum of either a Ra mutant (strain TV148) of strain LT2 or S. schottmülleri 8006 sharing the same O antigenic components with those of S. typhimurium induced only a short-lived protection in proportion to the number of L forms in the liver, and the protective immunity was lost before day 180 [3].

High impact information on Sox18

• Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice [4].
• Furthermore, we found no recombination between Sox18 and Ra in an interspecific backcross segregating for the Ra phenotype [4].
• We found point mutations in Sox18 in two different Ra alleles that result in missense translation and premature truncation of the encoded protein [4].
• We found that Sox18 is expressed in the developing vascular endothelium and hair follicles in mouse embryos [4].
• We previously mapped Sox18, encoding an SRY-related transcription factor, to distal mouse chromosome 2 [4].

Biological context of Sox18

• Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression [1].
• The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies [1].
• Examination of Sox18 expression during embryogenesis has shown that Sox18 is expressed transiently in endothelial cells of developing blood vessels, and mutations in Sox18 have been found to underlie the mouse vascular and hair follicle mutant ragged [5].
• In this study we have examined the expression of Sox18 in angiogenesis during wound healing [5].
• These results suggest that Sox18 directly and specifically stimulates mor gene expression, by trans-activating the mor DP enhancer [6].

Anatomical context of Sox18

• Sox18 expression was found five days after wounding during capillary sprouting in granulation tissue and persisted through the proliferative phase of healing, but was not detected in fully epithelialized wounds 21 days after wounding [5].
• Sox18 may therefore represent a transcription factor involved in the induction of angiogenesis during wound healing and tissue repair, but not in the maintenance of endothelial cells in undamaged tissue [5].
• Capillaries in the subcutaneous tissue of unwounded skin showed no Sox18 expression [5].
• The transcription factors, Sox17 (a Sry-related HMG box factor) and its upstream factors, Mixer (homeobox factor) and Casanova (a novel Sox factor), have been shown to function as endoderm determinants in Xenopus and zebrafish, respectively [7].
• Sox5 and Sox6 encode Sry-related HMG box transcription factors that act redundantly to promote chondroblast differentiation in all cartilages of the mouse embryo [8].

Associations of Sox18 with chemical compounds

• The rate of appearance (Ra) of glycerol, which indicates lipolytic rates, was similar at baseline and after 4 wk of CLA supplementation at rest (1.87 +/- 0.21 and 2.00 +/- 0.39 micromol/kg/min, respectively) and during exercise (7.12 +/- 0.74 and 6.40 +/- 0.99 micromol/kg/min, respectively) [9].
• 3H-3-glucose was infused for measurement of the glucose turnover rate (rate of appearance [Ra]) [10].

Physical interactions of Sox18

• In gel supershift assays, the Sox family member Sox18 bound directly to the multiple Sox consensus binding motifs of the mor DP enhancer [6].

Regulatory relationships of Sox18

• Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA [5].

Other interactions of Sox18

• Here, we provide direct evidence for redundant function of Sox17 and Sox18 in postnatal neovascularization by generating Sox17(+/-)-Sox18(-/-) double mutant mice [11].
• Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro [1].
• From the current data Ada can be taken as the proximal, and Ra as the distal gene marker of the imprinting region on the linkage map [12].
• The Sry-related HMG box transcription factor, Sox17, is required for formation of definitive endoderm that gives rise to various organs, including thyroid, lung, liver, pancreas, and intestine [13].
• Sequence and expression of Sox-18 encoding a new HMG-box transcription factor [14].

Analytical, diagnostic and therapeutic context of Sox18

• We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18 [1].
• Here we describe the analysis of Sox18(-/-) mice produced by gene targeting [15].
• Adoptive transfer of IHLs from immune-competent mice immunized with Ad-lacZ into Ragl-deficient mice previously infused with Ad-lacZ resulted in rapid elimination of beta-galactosidase-transduced hepatocytes [16].
• LPS did not affect I-Lep transport when studied by the brain perfusion method nor was Ob-Ra mRNA expression in isolated brain microvessels altered, demonstrating that a circulating factor rather than altered BBB function was responsible for inhibition [17].

References