Disease relevance of Chrna3

• Cell lines induced in two mouse strains with RadLV produced by the C6VL/1 thymoma all specifically utilize common V alpha 3 and V beta 8.2 variable region genes in the formation of a TCR structure [1].
• These data explain why alpha-3 and alpha-4 were not affected by the three independently induced deletion-type mutations that cause alpha-thalassemia in the mouse [2].
• Disruption of the connexin alpha 3 (Cx46) gene (alpha 3 (-/-)) in mice results in severe cataracts within the nuclear portion of the lens [3].
• To assess directly the functional role of the integrin VLA-3 (alpha 3 beta 1), we transfected human alpha 3 cDNA into erythroleukemia (K562) cells and rhabdomyosarcoma (RD) cells [4].
• Expression of alpha 3 beta 1, alpha 6 beta 1, or alpha V beta 1 did not induce bone metastasis [5].

High impact information on Chrna3

• These effects require alpha 3 beta 1 integrin-mediated binding of TIMP-2 to endothelial cells [6].
• We show that, in vivo, stem cells express higher levels of the alpha 2 beta 1 and alpha 3 beta 1 integrins than transit-amplifying cells and that this can be used both to determine the location of stem cells within the epidermis and to isolate them directly from the tissue [7].
• Fourth, an independently derived V alpha 3-expressing T cell clone (2C: alloreactive to Ld) showed a response to arsonate/Ld [8].
• We suggest that V alpha 3 encodes a protein sequence with a binding site for the arsonate hapten [8].
• Third, a V alpha 3-containing alpha chain (Ar-5: arsonate/I-Ad) transferred arsonate responsiveness to an appropriate recipient T cell (O3: ovalbumin/I-Ad) [8].

Biological context of Chrna3

• In this study, we show that the genes coding for the neuronal nicotinic acetylcholine receptor alpha 2, alpha 3 and beta 2 subunits are dispersed on three different mouse chromosomes, viz [9].
• We prepared a panel of mouse monoclonal antibodies specific for the A and B variants of the alpha 3 subunit to study their tissue distribution [10].
• The alpha subunits of the laminin-binding integrins alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1 have homologous sequences and are similar in structure [10].
• Recently, Kimura noted that the mouse globin pseudogene, psi alpha 3, evolved faster than the normal mouse alpha 1 gene, although he did not compute the substitution rate [11].
• The time course of adipogenesis declined from 7-10 days in controls to roughly 3 days in cultures treated with antisense-Gs alpha oligodeoxynucleotides, whereas oligodeoxynucleotides, antisense to Gi alpha 1, Gi alpha 3, and sense and missense to Gs alpha, had no such effect [12].

Anatomical context of Chrna3

• One of the alpha-tubulin isotypes described is expressed exclusively in testis and is encoded by two closely related genes (M alpha 3 and M alpha 7) which have homologous 3' untranslated regions but which differ at multiple third codon positions and in their 5' untranslated regions [13].
• Expression of the two variant forms of alpha 3 in K562 cells revealed that the ligand-binding specificities of alpha 3A beta 1 and alpha 3B beta 1 are identical: both bind human laminin-2 and -4, laminin-5, and laminins isolated from bovine kidney, but not bovine laminin-2 and -4, mouse laminin-1, or human fibronectin [10].
• The alpha 3 domain of the Qa-2 molecule is defective for CD8 binding and cytotoxic T lymphocyte activation [14].
• In IEC-6 cells, LPS caused an increase in the expression of alpha 3- and beta 1-integrins, a shift of beta 1-integrins from the cytoplasm to the plasma membrane and an increase in fibronectin bead adhesion during which beta 1-integrins accumulated underneath attached beads [15].
• RESULTS: Newborn intestinal injury was associated with decreased intestinal restitution and increased alpha 3- and beta 1-integrin expression in the ileal mucosa, which also was observed after LPS injection [15].

Associations of Chrna3 with chemical compounds

• While anabaseine has significant activity with muscle-type and neuronal alpha 3 beta 4 and alpha 4 beta 2 receptors, benzylidene anabaseine (BA) derivatives have high selectivity for the alpha 7 receptor subtype [16].
• Thus, a V alpha 3 gene segment, in conjunction with at least two different J alpha segments (J alpha 20'(Ar-5) and J alpha pHDS58(2C)) and at least three different beta chains (V beta 2(Ar-5), V beta 6(O3), and V beta 8(2C], confers reactivity to arsonate in association with at least three different MHC proteins (I-Ad, I-Ak, and Ld) [8].
• The T cell receptor V alpha 3 gene segment is associated with reactivity to p-azobenzenearsonate [8].
• CONCLUSIONS: Enterocyte migration is inhibited by LPS through increased expression and function of alpha 3- and beta 1-integrins [15].
• A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA receptors to a dopamine hyperfunction [17].

Physical interactions of Chrna3

• (5) the TcR alpha 3 loop interacts with the central portion of the peptide and stacks against the beta 2 loop [18].

Regulatory relationships of Chrna3

• Infection of L cells transfected with hybrid major histocompatibility complex class I molecules demonstrated that allelic control of susceptibility to MCMV mapped to the alpha 1 domain of Dd when in correct configuration with the alpha 2 and alpha 3 domains [19].
• The RA-induced expression of alpha 3 transcripts accounts for a comparably small number of nAChR-containing cells (< 20%) of which half coexpress alpha 4 transcripts [20].

Other interactions of Chrna3

• Chromosomal localization of the mouse genes coding for alpha 2, alpha 3, alpha 4 and beta 2 subunits of neuronal nicotinic acetylcholine receptor [9].
• This result extends the similarity between alpha 3, alpha 6, and alpha 7 laminin receptor subunits and suggests a common ancestral gene [21].
• Connexin alpha 3 (Cx46 or Gja3) gene targeted null mice developed lens nuclear cataracts shortly after birth [22].
• The Lama3 locus encoding the alpha 3 subunit of nicein was mapped distal to ataxia and did not recombine with Tg9257 [23].
• Segregation of restriction fragment length polymorphisms in backcross progeny of Mus musculus x Mus spretus mating confirmed this assignment and indicates that Atp4a and Atp1a3 (gene encoding the murine Na,K-ATPase alpha 3 subunit) are linked and separated by a distance of approximately 2 cM [24].

Analytical, diagnostic and therapeutic context of Chrna3

• In addition, the relative amounts of mRNA for the major nicotinic receptor subunits (alpha 4 and beta 2), as well as for three additional minor subunits (alpha 2, alpha 3, and alpha 5), were determined by in situ hybridization histochemistry followed by quantitation of image intensity [25].
• The isolated receptor was defined as the alpha 3 beta 1 integrin by immunoprecipitation with subunit-specific antibodies [26].
• SDS-PAGE of 3H-mannose-labeled I-Ak immunoprecipitates revealed that the alpha-chain peak was divided into three regions (alpha 1, alpha 2, and alpha 3), each of which migrated as a distinct individual band when isolated and reelectrophoresed [27].
• The mAb bound to murine (Mu) rIL-1 alpha 3 but not rMuIL-1 beta as assessed by both direct ELISA and immunoprecipitation [28].
• However, RR3-16 did not react with all T cell lines and clones known to express genes from the V alpha 3 family. cDNA sequences of three independent RR3-16+ T cell hybridomas analyzed by polymerase chain reaction were identical to the previously published V alpha 3 sequence of the CTL clone C9 [29].

References