Disease relevance of Cntn2

• Instead, although midline fusion was normal, selective fasciculation between commissural axons was inhibited, and TAG-1-labeled axons tangled bilaterally into Probst's bundles [1].
• These mice developed large granular lymphocytic leukemia, demonstrating that expression of Tax in the lymphocyte compartment is sufficient for the development of leukemia [2].
• Effects of the proteasome inhibitor PS-341 on tumor growth in HTLV-1 Tax transgenic mice and Tax tumor transplants [3].
• Of note, this skin disease completely resolved when Tax transgene expression was suppressed by administration of doxycycline, emphasizing the key role played by this viral oncoprotein in the observed pathology [4].
• In addition to the LTR of BLV, other viral enhancers, such as the enhancers of HTLV-1 and of mouse mammary tumor virus, which cannot be activated by wild-type BLV Tax protein, were activated by a Tax mutant protein [5].

High impact information on Cntn2

• After reaggregation with wild-type EGL precursor cells, weaver precursor cells extended neurites equivalent in length to wild-type cells, migrated along astroglial fibers, and expressed TAG-1 and astrotactin [6].
• Furthermore, we show that the localization of Caspr2 and clustering of K+ channels at the juxtaparanodal region depends on the presence of TAG-1, an immunoglobulin-like cell adhesion molecule that binds Caspr2 [7].
• Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule [8].
• In Tax transgenic mice, PS-341 administered thrice weekly inhibited tumor-associated NF-kappaB activity [3].
• TUNEL staining indicated that PS-341 treatment sensitizes Tax tumors to DNA fragmentation [3].

Chemical compound and disease context of Cntn2

• Transcriptional activation of the HTLV-I LTR has been demonstrated via a cyclic-AMP-responsive element within the 21-bp Tax-responsive elements of the LTR [9].

Biological context of Cntn2

• We used carbocyanine dye tracing to visualize thalamocortical and corticofugal projections as well as immunohistochemistry for L1 and TAG-1, respective markers of the two axonal systems, in wild-type, heterozygote, and null mutant for Emx2 at embryonic (E) ages ranging from E13.5 to E18 [10].
• These findings provide evidence that the TAG-1 protein is involved as a contact-dependent signal guiding not only axonal outgrowth but also cell migration [11].
• The perturbation of each region alone resulted in a complete loss of cell aggregation, suggesting that axonin-1-mediated cell-cell contact results from a cooperative action of two homophilic binding regions [12].
• In this report, we analyze the developmental phenotype of TAG-1-deficient animals in these two migratory systems [13].
• However, TAG-1 (-/-) mice showed the upregulation of the adenosine A1 receptors determined by [(3)H]cyclopentyl-1,3-dipropylxanthine in the hippocampus, and their greater sensitivity to convulsant stimuli than that in TAG-1 (+/+) mice [14].

Anatomical context of Cntn2

• Trigeminal ganglia were harvested from embryonic day 13.5 mouse embryos, and Bcl-2 and TAG-1 expression were measured by RT-PCR [15].
• TAG-1 expression was also examined in the embryonic trigeminal and dorsal root ganglia by immunohistochemistry [15].
• The adhesion molecule TAG-1 mediates the migration of cortical interneurons from the ganglionic eminence along the corticofugal fiber system [16].
• 5. In contrast with its mRNA, the protein was intensely detected on the fasciculated axons in the floor plates, ventral root, and dorsal funiculus in the E10.5-11.5 spinal cord and colocalized with NCAM and L1 on the ventral root and dorsal funiculus and partly colocalized with TAG-1 on the commissural axons and dorsal funiculus [17].
• In the E13.5-15.5 brain, RA175/TSLC1/SynCAM colocalized with NCAM and L1 on the developing thalamocortical fibers from the internal capsule (IC) and partly colocalized with TAG-1 on the cortical efferent axons in the intermediate zone (IZ) [17].

Associations of Cntn2 with chemical compounds

• TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus [14].
• Here, the expression of TAG-1/axonin-1 was investigated anatomically in the adult mouse brain by in situ hybridization using digoxigenin-labeled cRNA probes [18].
• The arising effects were even stronger than those coming from the overall suppression of the F3 or, respectively, TAG-1 genes, thus supporting the hypothesis that the mechanisms underlying axonal glycoprotein regulated expression are themselves endowed with a key significance in neural development [19].
• However, the effect of PS-341 on the growth of tumors in Tax transgenic mice revealed heterogeneity in drug responsiveness [3].
• Three general classes of receptor systems were analyzed, the neuron-glial adhesion ligand astrotactin, the neural cell adhesion molecules of the IgG superfamily, N-CAM, L1 and TAG-1, and the beta 1 subunit of the integrin family [20].

Regulatory relationships of Cntn2

• Netrin 1 promotes the exit of postmitotic migrating neurons from the embryonic lower rhombic lip and upregulates the expression of TAG-1 in these neurons [21].
• In a complementary model, transgenic mice have been generated which express the F3 cDNA under control of a selected regulatory region from the TAG-1 gene [19].

Other interactions of Cntn2

• These pathfinding defects were confirmed by immunohistochemistry for L1 and TAG1, markers of the early axonal connections [22].
• The elevated MATH1 levels appear to drive expression of a subset of early differentiation markers but are insufficient for development of a mature TAG-1-expressing granule cell [23].
• Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function [24].
• Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1 [7].
• Low levels of TAG-1/axonin-1 could be detected in cerebellar granule cells, in tufted and mitral cells of the olfactory bulb, and in pyramidal cells of area CA1 and CA3 of the hippocampus [18].

Analytical, diagnostic and therapeutic context of Cntn2

• Immunoprecipitation and cross-blocking with antiserum to TAG-1 suggested that OZ42 recognized the same molecule in the mouse cerebellum that has been described in embryonic rat and mouse spinal cord [25].
• Indeed, several studies have suggested that upregulation of various cellular oncogenes and cytokines by Tax may explain the pathogenesis observed in HTLV-I-infected individuals, as well as several Tax-transgenic animal models [26].
• These results demonstrate the activation of Tax-specific CD8+ T cells by vaccination and are supportive of a multivalent peptide vaccine approach against HTLV-1 infections [27].

References