Disease relevance of C3orf15

• There were no differences in toxicity between the two vectors when measured at matching levels of hAAT expression [1].
• An OAV vector which contained the cDNA of the human alpha1-antitrypsin (hAAT) gene linked to the Rous sarcoma virus promoter was generated and administered systemically to mice [2].
• Persistent expression of hAAT protein observed in BALB/cj SCID mice suggests that antigen-dependent immunity was essential for this apoptotic process in transduced Balb/c hepatocytes [3].
• In addition, while all strains had quantitatively comparable amounts of adenovirus genomes and hAAT mRNA transcripts in the liver 9 days posttransduction, only Balb/c mice had undetectable adenovirus vector genomes and hAAT mRNA in the liver 40 days posttransduction [3].
• In KC-depleted C57BL/6 and C3H mice increased and stabilized hAAT levels were observed following intravenous injection of HC-Ad vectors expressing human alpha-1 anti-trypsin (hAAT) either from the hAAT promoter or from the human cytomegalovirus promoter [4].

High impact information on C3orf15

• By injection of plasmid DNA encoding human alpha1-antitrypsin, significant concentrations of hAAT were detected in the serum of injected animals [5].
• Human alpha 1-antitrypsin (hAAT) was used as the reporter gene to facilitate long-term analysis of expression [6].
• AAT-1 and AAT-3 contain a cysteine residue in the second putative extracellular loop through which a disulfide bridge can form with a heavy chain [7].
• These results suggest that both AAT-1 and AMY-1 play roles in spermatogenesis [8].
• It was then found that AAT-1alpha weakly stimulated a phosphorylation activity of PKA and also that AAT-1 itself was phosphorylated by PKA in vivo and in vitro [8].

Biological context of C3orf15

• Only 60 amino acids in the C-terminal portion of AAT-1 derived from exons 15-17 are common among AAT-1L, AAT-1M, AAT-1S and AAT-1alpha [9].
• Interestingly, in the majority of animals of both strains depletion of KCs was sufficient to prevent the generation of anti-hAAT antibodies, resulting in prolonged transgene expression [4].
• The level and duration of hAAT gene expression was similar to that achieved with an hAd counterpart in both immunocompetent and immunodeficient mice [2].
• The combination of the hAAT promoter and four copies of the human apo E enhancer appears to be the expression cassette of choice for hepatocyte-specific overexpression of transgenes after gene transfer [10].
• In contrast to Balb/c mice, the loss of expression in C3H mice did not correlate with the loss of vector genomes or hAAT mRNA [3].

Anatomical context of C3orf15

• T cell hybridomas recognizing PiM and PiZ allelic forms of human alpha 1-antitrypsin (hAAT) each recognized both PiM 205-220 and PiM 335-350 [11].
• We found that MFP could induce the expression of hAAT protein in HeLa cells from 310 to 15,000 ng hAAT/10(6) cells/24 h, which was a 48-fold induction [12].
• Moreover, Huh7-E1 tumors release human alpha-1-antitrypsin (hAAT), which allows the monitoring of occult growing tumors (i.e. liver, peritoneum) by measuring serum hAAT levels [13].

Associations of C3orf15 with chemical compounds

• The levels of hAAT expression following tail vein infusions of 10(9) p.f.u. of Ad.RSV-hAAT were approximately four-fold higher in macrophage-depleted animals than in control animals pretreated with liposome-encapsulated phosphate-buffered saline (PBS) [14].
• Furthermore, the use of a liver cell-specific human alpha1-antitrypsin (hAAT)-promoter driving a tetracycline-controlled transcriptional silencer allowed specific protection of cells with hAAT-promoter activity in the absence of dox in vitro and in vivo, delineating a new principle of 'tissue protective' gene therapy [15].
• The consequences of macrophage depletion achieved by intravenous infusion of liposome-encapsulated clodronate (dichlormethylene diphosphonate (Cl2MDP)) on adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin (hAAT) gene were examined in 12-14-week-old male Balb/c mice [14].
• Two aspartate aminotransferase (EC 2.6.1.1) isoenzymes (AAT-1 and AAT-2) from Lupinus albus L. cv Estoril were separated, purified, and characterized [16].

Physical interactions of C3orf15

• All of the isoforms of AAT-1 were found to bind to and colocalized with AMY-1 in human cells [9].

Analytical, diagnostic and therapeutic context of C3orf15

• Gene transfer experiments were performed employing the hAAT gene, and the efficacy and differential identification in mouse plasma of human transgene versus mouse gene was assessed by ELISA and proteomic procedures, respectively [17].
• Southern analysis of extracted DNA and RT-PCR analysis of RNA from the liver reveal that hAAT gene is active and present as episomal form after 6 months [18].
• Expression in vitro did not predict in vivo performance: all vectors expressed hAAT at similar levels when tested in cell culture [19].
• The chimeric exon-intron complex in the middle of the naturally occurring hAAT exons II and III caused a 23-fold enhancement of hAAT expression in P. pastoris, measured through SDS-PAGE and immunoblot analyses [20].

References