Disease relevance of Kcnab2

• We found that strain differences significantly affected survival, body weight and thermoregulation in Kv beta2-null mice [1].
• The first peptide, for which the F5 TCR has a high affinity, derives from the influenza virus nucleoprotein (NP68) [2].
• In the present studies, the putative F5 protein-coding region was translated in vitro using a reticulocyte lysate system and in Escherichia coli, yielding a protein with the predicted molecular weight of 42 kDa [3].
• Greater than 95% of the CD8(+) T cells in F5 transgenic mice possess TCR specific for a peptide from influenza A virus expressed in the context of H-2D(b) [4].

High impact information on Kcnab2

• In the F5 transgenic mice, peptide injection in vivo leads to activation of most peripheral CD8+ T cells [5].
• Further administration of antigenic peptide to F5 mice results in the appearance of double-positive thymocytes that are resistant to Ag or anti-CD3-induced apoptosis [6].
• To determine whether deletion of immature thymocytes is the result of specific recognition of the antigenic peptide by the thymocytes or mature T cell activation, bone marrow chimeric mice were generated using a mixture of cells from F5 transgenic and nontransgenic mice [6].
• F5 transgenic mice, carrying a complete TCR-alphabeta transgene under the control of a CD2 minigene cassette on a C57BL/10 background, showed no age-associated thymic atrophy in any of the defined thymic subsets over the same period as the normal C57BL/10 mice [7].
• In this study we investigated further the molecular consequences of such interactions using F5 TCR transgenic mice and peptides previously shown to induce either negative or positive selection in the thymus [8].

Biological context of Kcnab2

• We tested the hypothesis that Bis1, a gene involved in seizure regulation in mice which has been localized to the distal part of chromosome 4, was the same as the gene Kcnab2, encoding the beta2-subunit for voltage-dependent K+ channels [9].
• DNA sequence analysis of the coding sequence for Kcnab2 from JE/Le mice revealed no structural alterations which might affect Kcnab2 function [9].
• Genetic modifiers of the Kv beta2-null phenotype in mice [1].
• The protein coding region of the F5 gene is approximately 16 kb in length and is composed of 13 coding exons [10].
• Expression of the T-lymphocyte activation gene, F5, by mature neurons [11].

Anatomical context of Kcnab2

• Tissue specificity and sequence conservation suggest an important function for F5 in T-lymphocyte proliferation and neuronal maturation [10].
• F5 is a novel mRNA selectively expressed by proliferating lymphocytes and mature neurons [12].
• F5 mRNA was detected in the central nervous system, peripheral nervous system, and retina in cells having the location and morphological features of neurons [11].
• In previous studies, differential hybridization screening of an activated murine T-lymphocyte cDNA library identified an interleukin 2-responsive mRNA, designated F5, expressed in lymphoid tissues and brain only [12].
• On Northern blotting, F5 mRNA was expressed in adult mouse brain, spinal cord, eye, and dorsal root ganglia but not in peripheral nerve [12].

Associations of Kcnab2 with chemical compounds

• In contrast, RU486 had no effect on thymic apoptosis induced by the influenza A nucleoprotein NP366-374 peptide, recognized in context of Db, in F5 TCR transgenic mice [13].
• The results of temperature-dependent phase separation with Triton X-114 and alkaline extraction with sodium carbonate of the P2 and P3 fractions were consistent with the F5 protein being an extrinsic membrane-associated protein [14].
• The enzyme was able to hydrolyse bradykinin at the G4-F5 peptide bond and was inhibited by thiorphan [15].

Other interactions of Kcnab2

• Two facts suggested this hypothesis: Kcnab2 is located in the 3.1-cM confidence interval containing Bis1 and many studies have shown an involvement of K+ channels in the genesis of seizures [9].
• Kv beta2 is the predominant Kv beta subunit in the mammalian nervous system, but its functions in vivo are not clear [1].
• Kv beta1.1/Kv beta2 double knockouts had significantly increased mortality compared with either single knockout but still maintained surface expression of Kv1.2, indicating that trafficking of this alpha subunit does not require either Kv beta subunit [1].
• High-resolution mapping of the genes Kcnb3 and Ly63 on distal mouse chromosome 4 [16].

Analytical, diagnostic and therapeutic context of Kcnab2

• To specifically test whether Kv beta1 is a genetic modifier of the Kv beta2-null phenotype, we generated Kv beta1.1-deficient mice by gene targeting and bred them to Kv beta2-null mice [1].
• Combined in situ hybridization histochemistry for F5 mRNA and immunofluorescence staining for cell-specific markers confirmed that neurons expressed F5 mRNA but astrocytes did not [11].
• In the present studies, the intracellular localization of the F5 protein in adult mouse brain was determined by subcellular fractionation and Western blotting [14].
• This system provides a useful bioassay for identifying the component peptides of thymosin F5 which promote thymocyte differentiation and/or maturation and for elucidating the mechanisms of action of the biologically active thymosin peptides [17].
• Likewise, upon adoptive transfer into wild-type mice, TCDD suppressed the expansion and differentiation of F5-derived CD8(+) T cells [4].

References