Disease relevance of TNXB

• CONCLUSION: TNXB and TNC may be involved in the malignant transformation of plexiform neurofibromas [1].
• Sequencing of phage and cosmid clones and of cDNA fragments shows that the XB gene spans 65 kb of DNA, consisting of 39 exons that encode a 12-kb mRNA [2].
• Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition [3].
• Of 17 cell types and lines screened, TNXB expression was abundant only in fibroblasts and HT1080 human skin fibrosarcoma cells [4].
• Microarray-Based Identification of Tenascin C and Tenascin XB, Genes Possibly Involved in Tumorigenesis Associated with Neurofibromatosis Type 1 [1].

High impact information on TNXB

• This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts [3].
• Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B [2].
• RNase protection experiments show that the TN-X transcript is expressed ubiquitously in human fetal tissues, with the greatest expression in the fetal testis and in fetal skeletal, cardiac, and smooth muscle [2].
• Carriership of a defective tenascin-X gene in steroid 21-hydroxylase deficiency patients: TNXB -TNXA hybrids in apparent large-scale gene conversions [5].
• We identify the principal TN-X promoter and a previously unknown 5' untranslated exon that lies more than 10 kb upstream from the previously known exons [6].

Biological context of TNXB

• 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 [7].
• The occurrence of defective CYP21 genes, including 15 mutations, has been attributed to intergenic recombination of DNA sequences from CYP21P, and shows no influence on the RP1-C4A-CYP21P-XA-RP2-C4BCYP21- TNXB gene locus on chromosome 6p21 [8].
• Here, we describe an established PCR-based amplification method to analyze directly a CAH patient with a single CYP21 deletion, followed by RFLP analysis to characterize the interconversion region between tenascin A (TNXA) and tenascin B (TNXB) [9].
• To replicate the initial finding, we analysed two positive single nucleotide polymorphisms (SNPs), rs1009382 and rs204887 present at the TNXB locus, in a Chinese population by using PCR-based restriction fragment length polymorphism analysis [10].
• These findings suggest that both elastic fiber abnormalities and reduced collagen content contribute to the observed phenotype in TNX-deficient patients [11].

Anatomical context of TNXB

• A similar pattern of TN-X expression, first in connective tissue surrounding muscle, and then by a subset of cells within muscle, was seen in para-axial, body wall, craniofacial, and appendicular muscle [12].
• After the epicardium is complete, TN-X is expressed in the sub-epicardial space in association with developing blood vessels, and later by non-myocytes dispersed through the myocardial wall [12].
• Using an 800 bp cDNA encoding the fibrinogen-like domain of TN-X, we show that TN-X expression begins in migrating cells of the epicardium in the E12 heart [12].
• TN-X is also highly expressed in the interdigital space at E15 and surrounding developing tendons, suggesting an additional role in cell fate determination [12].
• Indirect genetic evidence in humans suggests an essential function for TN-X, and the pattern of TN-X expression in heart, skeletal muscle, and limb is consistent with this hypothesis [12].

Associations of TNXB with chemical compounds

• The complete genomic DNA sequence between C2 and TNX is now available [13].
• A deletion or duplication of a C4 gene is always accompanied by its neighboring genes, RP at the 5' region, and CYP21 and TNX at the 3' region [13].
• The reaction to SSA but not to MAM suggested the presence of sialic acid linked alpha2,6 to galactose in both cellular and serum TNX [14].

Other interactions of TNXB

• Because the TNXB gene is less than 100 kb away from the NOTCH4 locus that was also reported to be associated with schizophrenia, allelic and locus heterogeneity could be possible reasons for the failure to replicate the TNXB finding [10].
• Expression of TNXB promoter/reporter constructs in HT1080 cells showed that region E, near the untranslated exon, had the greatest activity, and the two regions of greatest identity, 5.0 and 3.3 kb upstream, had no activity [4].

Analytical, diagnostic and therapeutic context of TNXB

• It has been demonstrated that a PCR product amplified with allele-specific primers covering tenascin B ( TNXB) to the 5' end of the CYP21 gene combined with Southern analysis by Ase I and Nde I digestion may be used for identifying the chimera in the CYP21 gene [15].

References