Disease relevance of TNXA

• Deficiency of TNX causes a recessive form of Ehlers-Danlos syndrome characterized by joint hypermobility, skin fragility and hyperextensible skin [1].
• FSaII fibrosarcoma cells grown in the hind limb of female C3H mice were used to study the effect of TNX on tumor blood perfusion and oxygenation [2].
• Toxicity of hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) to earthworm was evaluated [3].
• The TNX group showed small, but significant, decreases in lordosis latencies postoperatively [4].
• Because of the reported cardiovascular abnormalities in other EDS types and the excessive haematoma formation after mild trauma in TNX-deficient individuals, we investigated whether cardiovascular or coagulation abnormalities occur in these patients [5].

High impact information on TNXA

• We describe a new contiguous-gene syndrome, involving the CYP21B and TNX genes, that results in 21-hydroxylase deficiency and a connective-tissue disorder consisting of skin and joint hyperextensibility, vascular fragility and poor wound healing [6].
• The abundant expression of TNX in connective tissues is consistent with a role in EDS, and our patient's skin fibroblasts do not synthesize TNX protein in vitro or in vivo [6].
• His paternal allele carries a novel deletion arising from recombination between TNX and its partial duplicate gene, XA, which precludes TNX synthesis [6].
• Human populations are endowed with a sophisticated genetic diversity of complement C4 and its flanking genes RP, CYP21, and TNX in the RCCX modules of the major histocompatibility complex class III region [7].
• To determine how this locus was duplicated, we sequenced the DNA at the duplication boundaries and the 7 kb between P450c21A and C4B comprising the XA locus [8].

Chemical compound and disease context of TNXA

• Toxicity of the explosive metabolites hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) and hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) to the earthworm Eisenia fetida [3].

Biological context of TNXA

• Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover between TNXA from a bimodular chromosome and TNXB from a monomodular chromosome [9].
• Modular variations of the human major histocompatibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease associations [9].
• Absence of the truncated genes RP2 and Gene XA have been detected in genomes with single RCCX modules [10].
• Sequences promoting the transcription of the human XA gene overlapping P450c21A correctly predict the presence of a novel, adrenal-specific, truncated form of tenascin-X [11].
• RNase protection assays, cDNA cloning, and RT/PCR show that adrenal cells contain a novel transcript, termed short XB (XB-S), which has the same open reading frame as TN-X.(ABSTRACT TRUNCATED AT 250 WORDS)[11]

Anatomical context of TNXA

• Nevertheless, XA is transcribed into a stable 2.6-kb polyadenylated RNA that is expressed uniquely in the adrenal gland [8].
• This complex locus is duplicated into A and B loci, so that the organization is 5'-C4A-21A-XA-C4B-21B-XB-3'. Although this duplication event truncated the 65-kb X(B) gene to a 4.5-kb XA gene, the XA gene is transcriptionally active in the adrenal cortex [11].
• Although the precise role of TNX in the pathogenesis of EDS is uncertain, this patient's findings suggest a unique and essential role for TNX in connective-tissue structure and function [6].
• Skin of TNX deficient patients shows abnormal elastic fibers and reduced collagen deposition [1].
• Tenascin-X (TNX) is a large 450 kDa extracellular matrix protein expressed in a variety of tissues including skin, joints and blood vessels [1].

Associations of TNXA with chemical compounds

• As shown by definitive RFLPs, the tandemly arranged genes RP, C4, CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module [9].
• It contains the functional gene steroid CYP21A, long stretches of repetitive DNA elements, and three partially duplicated gene segments TNXA, SKI2W2 and RP2 [12].
• When carbogen breathing was begun immediately after TNX injection, no further reduction occurred in tumor blood perfusion at 2 hours after injection [2].
• PURPOSE: To investigate the effect of arsenic trioxide, Trisenox (TNX), on primary cultures of endothelial cells and tumor tissue under varying pH and pO(2) environments and the effects of combined TNX and radiation therapy on experimental tumors [2].
• Evaluating the bioavailability of explosive metabolites, hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX), in soils using passive sampling devices [13].

Other interactions of TNXA

• The sequences beyond--1524 nt may be completely different as the C4 genes at RCCX module I have RPI-specific sequences, while those at Modules II, III and IV have TNXA-specific sequences [14].
• PCR-based detection of the CYP21 deletion and TNXA/TNXB hybrid in the RCCX module [15].

Analytical, diagnostic and therapeutic context of TNXA

• Absence of TNX mRNA and protein in the proband, mapping of the TNX gene and HLA typing of this family suggest recessive inheritance of TNX deficiency and connective-tissue disease [6].
• RESULTS: A single intraperitoneal injection of 8 mg/kg TNX reduced the blood perfusion in FSaII tumors by 53% at 2 hours after injection [2].
• METHODS AND MATERIALS: Human dermal microvascular endothelial cells were cultured in vitro and exposed to TNX under various combinations of aerobic, hypoxic, neutral, or acidic conditions, and levels of activated JNK MAP kinase were assessed by Western blotting [2].
• The effect of adsorption filtration of leukocyte-reduced single donor platelet (SDP) units collected on a CS-3000+ with a TNX chamber was compared to filtration of SDP units prepared via an isoradial chamber [16].
• Serum levels of TNX were analysed using high performance liquid chromatography [17].

References