大鼠肝癌中α—抑制因子3基因表达及基因结构的...

The expression and structure of alpha 1-inhibitor 3 (alpha 1-I3) gene were investigated in 16 primary rat hepatomas induced by diethylnitrosamine. In most tumor samples (75%, 12/16), the expression of alpha 1-I3 gene manifested markedly diminished or undetectable level of alpha 1-I3 mRNA. Further study indicated that the abnormal expression of alpha 1-I3 gene in the hepatomas examined might be due to, at least in part, the gene hypermethylation, insertion of repeat sequence(s) or base substitutions at the recognition sequences of some restriction endonucleases which caused certain alteration in the gene structure. The significance of alpha 1-I3 as an endogenous antitumor factor in hepatocarcinogenesis was also discussed.     

The structure of the human CD2 gene and its expression in transgenic mice.

We report the genomic organization of the human CD2 gene and its expression in transgenic mice. A 28.5 kb segment of DNA consisting of 4.5 kb 5' flanking sequences, 15 kb containing the gene's five exons and 9 kb of 3' flanking sequences can direct the expression of the CD2 gene only on thymocytes, circulating T cells and megakaryocytes of the transgenic mice. The expression of each copy of the human CD2 transgene appears to be as high as the endogenous mouse CD2 gene and as high as the expression on the surface of human T lymphocytes, independent of the site of integration and dependent on the copy number of genes that have integrated.     

The structure of the human LIM protein ACT gene and its expression in tumor cell lines

We describe the human ACT genomic and cDNA sequence which like its murine counterpart contains the defining secondary structure of the FHL (Four-and-a-Half LIM-domain) LIM-protein family. The coding region of the human ACT gene spans five exons. This distribution is very similar to the FHL1 gene and includes the arrangement of split codons across exon boundaries suggesting that these genes share a common ancestor. The human ACT gene was not detected by Northern analysis in the adult testis although this is the only known site of expression found with its murine counterpart. However, the human ACT gene was found to be expressed in a panel of human tumor cell lines derived from squamous cell carcinomas, melanomas, and leukemias. Interestingly, FHL1, FHL2, and FHL3 were also found to be expressed in some of these cell lines and the results suggest an important role for FHLs in tumor biology.     

The structure and expression of the preproenkephalin gene.

Enkephalins are pentapeptides with opioid activity which are found in a wide variety of tissues. Studies of enkephalin-containing peptides from the adrenal gland have established that the mature pentapeptides are derived by proteolytic processing of a precursor protein. We have shown that human adrenal medullary tumours contain mRNA which can be translated in vitro to yield a single major enkephalin precursor. The sequence of cloned cDNA shows that the preproenkephalin mRNA encodes four copies of met-enkephalin, two copies of met-enkephalin extended sequences and one copy of leu-enkephalin; each copy is flanked by paired basic amino acids which are presumably recognised by the processing protease. We have used the cloned human cDNA as a hybridisation probe to detect the corresponding mRNAs in rat adrenal gland and, in smaller amounts, in rat brain. We have been unable to detect in brain any other cross-hybridising mRNAs which might encode other putative precursor proteins.     

Evolutionary aspects, structure, and expression of the rat interleukin 4 gene

The rat interleukin 4 (IL 4) gene has been isolated from a genomic lambda phage library by cross-hybridization to the mouse IL 4 cDNA. Like the mouse and human counterparts, it exists as a single copy gene in the genome and consists of four exons. The overall structure of the IL 4 locus seems highly conserved. This is indicated by the low degree of restriction fragment length polymorphism in a number of laboratory and wild mice and by the conservation of the intron size between human, rat, and mouse IL 4 genes. Furthermore, evolutionary conserved elements are the promoter region, the position of cysteine residues and sequence motifs in the 3' untranslated regions that are believed to be involved in destabilization of the mRNA. In contrast, the predicted amino acid sequence of the rat IL 4 gene shows low homology (57%) with the mouse homologue. The divergence between mouse and rat IL 4 genes is even more pronounced in the carboxy-terminal region (47% homology in the last 68 amino acids). The ratio between replacement and silent mutations in the IL 4 genes of different species suggests a complex pattern of selective forces acting on the IL 4 gene, which includes both selection against and for amino acid substitutions in individual positions. The functional identity with IL 4 has been confirmed by expression of the gene and the demonstration of the ability to induce MHC class II antigen expression on spleen cells.     

The structure and expression of the human neuroligin-3 gene

The neuroligins are a family of proteins that are thought to mediate cell to cell interactions between neurons. During the sequencing at an Xq13 locus associated with a mental retardation syndrome in some studies, we discovered a portion of the human orthologue of the rat neuroligin-3 gene. We now report the structure and the expression of that gene. The gene spans approximately 30kb and contains eight exons. Unlike the rat gene, it codes for at least two mRNAs and at least one of which is expressed outside the CNS. Interestingly, the putative promoter for the gene overlaps the last exon of the neighboring HOPA gene and is located less than 1kb from an OPA element in which a polymorphism associated with mental retardation is found. These findings suggest a possible role for the neuroligin gene in mental retardation and that the role of the gene in humans may differ from its role in rats.