SEARCH · PubMed Health

Results for “reference mapping”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources

PubMed1991

Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: analysis with multiple breakpoint probes.

Centrocytic lymphoma is a B-cell non-Hodgkin's lymphoma (NHL) composed of lymphocytes resembling cleaved follicular center cells (centrocytes). Previous studies have suggested an association between t(11;14) chromosomal translocations and bcl-1 rearrangement in centrocytic and related intermediate lymphocytic lymphomas. To further characterize the association between bcl-1 and centrocytic lymphoma, Southern blot analysis was performed on samples from 23 patients using four separate bcl-1 breakpoint probes spanning 63 kb of the chromosome 11 bcl-1 locus. Rearrangements were identified in six patients with the major translocation cluster (MTC) probe and in another six with probe p94PS, located about 24 kb 5' of MTC. Eleven of these 12 cases showed comigration of rearranged bcl-1 and Ig heavy chain-joining genes, consistent with the t(11;14) chromosomal translocation. No rearrangements were observed with the bcl-1 locus probes p210 or p11EH located 5' of p94PS, nor with bcl-2 or c-myc oncogene probes. No bcl-1 rearrangements were identified in B-cell follicular NHL (15), small noncleaved cell (Burkitt's and non-Burkitt's) NHL (8), T-cell NHL (4), multiple myeloma (14), and pre-B-cell acute lymphoblastic leukemia (9). One of 23 B-cell NHL of large cell type and one of 19 chronic lymphocytic leukemias or small lymphocytic NHL had MTC rearrangement. Thus, bcl-1 rearrangement occurred at MTC or p94PS in 12 of 23 centrocytic lymphomas (52%), confirming a nonrandom association and suggesting a pathogenetic role for the bcl-1 locus in this immunohistologic subtype of NHL.

Blotting, Southern↗

PubMed1990

Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type.

Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase (b5R) deficiency. In an attempt to clarify the molecular mechanisms involved in the enzyme deficiency, we isolated the b5R gene from a patient homozygous for hereditary methemoglobinemia, generalized type, and compared its nucleotide sequence with that of the normal NADH-cytochrome b5R gene. Only one difference was observed; a thymidine at the first position of codon 127 (TCT) was altered to a cytidine in the b5R gene of the patient, resulting in replacement of serine with proline. Dot blot hybridization of the amplified DNA samples with allele-specific oligonucleotide probes showed that the proband and her brothers were homozygous for this mutation and that their father was heterozygous. Although the activity of b5R in lymphoblastoid cells from homozygotes was reduced to 10% of the normal level, RNA blot and protein blot analyses of the lymphoblastoid cells showed that synthesis of b5R messenger RNA and the b5R polypeptide were normal. Serine at residue 127 is presumed to be in an alpha-helix structure that is part of a nucleotide-binding domain. These observations suggest that replacement of Pro-127 causes a significant conformation change in the nucleotide-binding domain that affects electron transport from NADH to cytochrome b5. Functional enzyme deficiency results in a generalized type of hereditary methemoglobinemia.

Adult↗

PubMed1990

Identification of a chromosome 6-encoded dystrophin-related protein.

Dystrophin is the protein product of an X-linked locus which is disrupted to yield the phenotypes of Duchenne and Becker muscular dystrophies. Recently an autosomal transcript was identified (Love, D. R., Hill, D. F., Dickson, G., Spurr, N. K., Byth, B. C., Marsden, R. F., Walsh, F. S., Edwards, Y. H., and Davies, K. E. (1989) Nature 339, 55-58) with a carboxyl-terminal sequence similar to dystrophin. We have isolated part of this chromosome 6-encoded cDNA by polymerase chain reaction cloning and expressed it as a recombinant bacterial protein. Antibodies against this recombinant protein detected a large protein that exactly co-migrates with dystrophin yet is detectable in patients suffering from Duchenne and Becker muscular dystrophies. This protein of similar size to dystrophin may play a functional role similar to dystrophin, but unlike dystrophin, the protein is detected in tissues other than muscle and nerve. This newly identified protein is presumably a member of the spectrin/alpha-actinin/dystrophin family of proteins.

Base Sequence↗

PubMed1990

A missense mutation at Ile172----Asn or Arg356----Trp causes steroid 21-hydroxylase deficiency.

Congenital adrenal hyperplasia (CAH) is a common recessive genetic disease caused mainly by steroid 21-hydroxylase (P450c21) deficiency. Many forms of CAH exist resulting from various mutations of the CYP21B gene. We sequenced CYP21B cDNA from a normal person and its genes from a patient with simple virilizing CAH. When comparing several CYP21B sequences, we found it was polymorphic. In the patient, a single base substitution replaced Ile172 (ATC) with Asn (AAC) in one allele while Arg356 (CGG) was converted to Trp (TGG) in the other. A normal P450c21 cDNA clone was transfected into COS-1 cells to produce 21-hydroxylase activity toward its substrates, progesterone and 17-hydroxyprogesterone. Mutants corresponding to Asn172 or Trp356 mutation were constructed by site-directed mutagenesis of the normal c21 cDNA clone. They failed to produce active enzyme toward either substrate upon transfection into COS-1 cells, demonstrating that these mutations caused CAH. Aligning sequences with other P450s, Ile172 could be located in the membrane anchoring domain and Arg356 in the substrate-binding site of P450c21. Both mutations are present in the CYP21A1P pseudogene, suggesting that they may be transferred from CYP21A1P by gene conversion events.

Adolescent↗

PubMed1990

Analyses of catalytic activity and inhibitor binding of human acid beta-glucosidase by site-directed mutagenesis. Identification of residues critical to catalysis and evidence for causality of two Ashkenazi Jewish Gaucher disease type 1 mutations.

Analyses of catalytic properties and inhibitor binding were conducted to investigate the molecular basis of active site function of human acid beta-glucosidases (EC 3.2.1.45) expressed from normal and Gaucher disease Type 1 alleles. Comparative studies were conducted with enzymes expressed from natural (spleen and fibroblasts) alleles or from mutagenized cDNAs in Spodoptera frugiperda (Sf9) cells using the baculovirus expression system. Mutant cDNAs containing Thr43 to Lys43 (beta-GlcThr43----Lys) and Asp358 to Glu358 (beta-GlcAsp358----Glu) substitutions and two cDNAs containing Ashkenazi Jewish Gaucher disease Type 1 mutations, Arg120 to Gln120 (beta-GlcArg120----Gln) and Asn370 to Ser370 (beta-GlcAsn370----Ser) were expressed and the gene products characterized by enzymatic, immunologic, and inhibitor studies. Genotypes at the acid beta-glucosidase locus in selected Gaucher disease Type 1 patients were determined by allele-specific oligonucleotide hybridization of amplified genomic DNA. Compared with normal, recombinant or natural enzymes expressed from beta-GlcAsn370----Ser alleles had about 2-5-fold decreased specific activity based on CRIM (cross-reacting immunologic material). The beta-GlcArg120----Gln cDNA expressed catalytically inactive CRIM in Sf9; consistent with the 9-fold decreased CRIM-specific activity of the natural enzyme from a beta-GlcArg120----Gln/beta-GlcAsn370----Ser genetic compound. The beta-GlcAsp358----Glu cDNA expressed catalytically inactive CRIM in Sf9 cells. The presence of natural or recombinant enzyme expressed from beta-GlcAsn370----Ser alleles was sufficient to confer 3-5-fold increased IC50 values for deoxynojirimycin, glucosylsphingosine, and N-alkyl-glucosylamine derivatives. Progress curves for inhibition by the slow-tight binding N-alkyl-glucosylamines indicated that the beta-Glc-Asn370----Ser mutation did not alter a conformational change induced by these reaction intermediate analogues. These results provide evidence that the beta-GlcArg120----Gln and beta-GlcAsn370----Ser mutations found in Gaucher disease Type 1 patient genomes are the molecular bases of the enzymatic dysfunction. In addition, the region including Arg120 and that encompassing Asp358 and Asn370 contain residues critical to active site formation or participation in the catalytic mechanism.

Amino Acid Sequence↗

PubMed1990

Structural and functional characterization of a splicing mutation in the pro-alpha 2(I) collagen gene of an Ehlers-Danlos type VII patient.

A splicing mutation in the pro-alpha 2(I) collagen gene of a patient with Ehlers-Danlos syndrome type VII has been characterized. Protein microsequencing of peptides prepared from the patient's dermal collagen identified an interstitial deletion of 18 residues. The deleted segment corresponds to the amino-terminal telopeptide junction domain encoded by the sixth exon of the pro-alpha 2(I) collagen gene. Sequencing of specifically primed cDNA clones confirmed the presence of two distinct populations of pro-alpha 2(I) mRNAs, a normal one and another which lacks the sequences of exon 6. Limited sequencing of genomic clones showed that one of the pro-alpha 2(I) alleles displays a conservative change in the seventh codon of exon 6 (GAC for GAT), and a base substitution at position +1 of intron 6 (A for G). Since the normal transcript contains the GAT codon, the intronic change was associated with the allele that gives rise to the shortened pro-alpha 2(I) collagen mRNA. The two allelic fragments were subcloned into an expression vector and the pattern of splice-site selection for exons 5-8 was assessed for each of the constructs after transfection into COS cells. This documented skipping of exon 6 sequences only in transcripts of the minigene construct that harbors the G to A transition. Expression of allelic cross-constructs confirmed that the single-base substitution at position +1 of intron 6 is the mutation responsible for the abnormal joining of exons 5 and 7 sequences in the patient's shortened pro-alpha 2(I)mRNA.

Alleles↗

PubMed1989

Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase.

Adenylate kinase deficiency in the erythrocyte is a rare genetic disorder associated with hemolytic anemia. To determine the molecular basis of this disorder, we first cloned the normal gene encoding human cytosolic adenylate kinase (AK1) and determined the structure. The gene was 12 kilobase pairs long and was split into 7 exons. The structures of 5'- and 3'-flanking regions were determined by primer extension and RNA blot analysis. The results showed that two species of mRNA with 0.9 and 2.5 kilobases, which differed at the 3'-end portion, were generated by the AK1 gene. Alu sequences were found in the largest intron (intron 5) and in the noncoding region of exon 7. Next, both alleles of the AK1 gene were cloned from DNA of a patient bearing the adenylate kinase deficiency and their nucleotide sequences determined. A transition (C----T) was found in exon 6 on an allele, which resulted in an Arg to Trp (CGG----TGG) substitution at the 128th residue of AK1. Since chicken AK1 is highly homologous to human AK1 with respect to the amino acid sequence, we introduced an Arg to Trp substitution to chicken AK1 at the same position by oligodeoxynucleotide-directed mutagenesis. The mutant chicken AK1 expressed in Escherichia coli showed a reduced catalytic activity as well as a decreased solubility and a change in affinity to phosphocellulose. Thus it was considered that the observed C----T transition was a cause of the decreased AK1 activity of the patient's erythrocyte. Analysis on phosphocellulose chromatography of erythrocyte AK1 of the patient and parents revealed that the patient's mutant allele was derived from the mother.

Adenylate Kinase↗

PubMed1989

Kinetics of induction by thyroid hormone of the two hepatic mRNAs coding for cytosolic malic enzyme in the hypothyroid and euthyroid states. Evidence against an obligatory role of S14 protein in malic enzyme gene expression.

In rat liver, triiodothyronine (T3) and dietary carbohydrate induce the expression of the genes coding for malic enzyme (ME) (EC 1.1.1.40) and S14 protein. The mRNAs for both ME and S14 are elevated under circumstances associated with augmented lipogenesis. Since the lag time in the induction of mRNA coding for S14 is short (20 min) and the lag time in the induction of the mRNA for ME is relatively long (2-6 h), the possibility arose that the induction of the ME gene by T3 was mediated by S14 protein. To test this hypothesis we examined the temporal relationship between the accumulation of the hepatic S14 protein and the mRNAs coding for ME. In confirmation of previous reports, we found that two mRNAs coded for ME, one 27 S and the other 21 S in size. The level of enzyme activity generated appeared to be determined by both mRNA species. Sequencing of the 27 S fragment established that this mRNA is generated as a consequence of the use of an alternate polyadenylation site downstream to that used in the 21 S mRNA. Unanticipated from the earlier descriptions was the finding of a markedly asynchronous response of these mRNAs to T3 in hypothyroid animals. The lag time following T3 administration was 90 min for the 27 S and fully 8-12 h for the smaller 21 S sequence. Despite the rapid rise of mRNA S14, the S14 protein could not be detected for approximately 12 h after T3 administration. This ruled out the possibility that S14 is an obligate mediator in the induction of the ME gene. A contrasting pattern was observed in the euthyroid state where both ME mRNAs had indistinguishable lag times of 2-3 h, and the S14 protein rose within the same time frame. The delayed response of the 21 S mRNA for malic enzyme in hypothyroid animals thus appears to be due to a reversible defect in the transcription of the ME gene.

Animals↗

PubMed1989

Expression of the rat L-type pyruvate kinase gene from its dual erythroid- and liver-specific promoter in transgenic mice.

The gene for the L-type pyruvate kinase possesses two promoters which are located 500 base pairs apart. The L promoter is specific to liver and regulated by hormones and diet; the L' promoter is specific to erythroid cells. We produced two series of transgenic mice carrying either the entire rat L-pyruvate kinase gene or a minigene devoid of exons two to nine, with 2.7 kilobases of flanking sequences 5' to the cap site of the L' promoter and 1.4 kilobases 3' to the downstream polyadenylation site. In both series the patterns of expression from the two promoters were similar to those of the endogenous rat gene. The rat L promoter was expressed strongly in liver and weakly in kidney and gut of adult transgenic mice. Moreover, it was regulated like the endogenous rat L-pyruvate kinase gene upon hormonal and nutritional adaptation: the level of L-pyruvate kinase mRNA was decreased dramatically by 24 h of starvation, while refeeding a carbohydrate-rich diet strongly stimulated expression of the transgenes. This stimulation was prevented by glucagon. Use of alternative polyadenylation sites in the last exon of the rat L-type pyruvate kinase gene was similar for both types of transgenes and similar to that in rat and not control mice, suggesting that the transgenes contain the sequences that control the choice of polyadenylation site. Transcription of the minigene was higher than that of the entire transgene, probably due to the high copy number of the minigene. At the protein level, rat L subunits encoded by the entire transgene were more abundant than mouse subunits in the liver of adult transgenic mice. In contrast, expression of the rat L' promoter in fetal liver was only 5% of that in fetal rat liver, and we were unable to detect rat L' subunits of pyruvate kinase enzyme in the red blood cells from transgenic mice. Our results suggest that the integrated DNA contains all elements necessary for tissue specificity (L' and L) as well as hormonal and nutritional control (L) of expression of the rat transgene. Nevertheless, a L'-specific activating element may be missing.

Animals↗

PubMed1989

An initiation codon mutation in the apoC-II gene (apoC-II Paris) of a patient with a deficiency of apolipoprotein C-II.

We have identified the genetic defect that leads to a deficiency of apoC-II in the proband from the Paris kindred. Analysis of the apoC-IIParis DNA by Southern blot hybridization revealed no major gene rearrangements, but sequencing of polymerase chain reaction-amplified apoC-IIParis DNA revealed an A to G transition that changed the initiation AUG (methionine) codon to GUG (valine). Potential initiation of translation at the closest inframe methionine codon eliminates the entire signal peptide and the first 8 amino-terminal residues of apoC-II which would prevent apoC-II secretion into plasma. In agreement with this, no apoC-II was detected in the patient's plasma by radioimmunoassay or by two-dimensional gel electrophoresis and immunoblotting. Direct sequencing of amplified patient DNA from 12 different polymerase chain reaction samples demonstrated the presence of the A to G substitution in all, indicating that the proband is a homozygote for the defect. We propose that in the apoC-IIParis gene, a mutation in the initiation methionine codon prevents the normal initiation of apolipoprotein synthesis and leads to a deficiency of apoC-II. This initiation methionine mutation represents a new type of molecular defect that can result in Type I hyperlipoproteinemia.

Adult↗

PubMed1989

Circulating immune complexes (CIC) in Hodgkin's disease. I. Levels and two-dimensional analysis.

A polyethylene glycol 6000 (PEG) mediated precipitation procedure was used to estimate the levels of CIC in sera of healthy donors and patients with Hodgkin's disease (HD). In comparison with the normal serum samples, sera from untreated HD patients showed elevated CIC levels scattered over a wider range and a mean which differed significantly. Sera from treated patients who were in clinical remission exhibited decreased CIC levels. However, the mean level in this category was still above the mean found in the normal sera. The analysis of the data showed that the sera from HD patients in Stage I and II, and with LP and MC type histology showed preferential increase in CIC levels. The analysis of these CICs in 2D-SDS-PAGE and a careful scrutiny of the polypeptide patterns obtained revealed significantly elevated amounts of a component with a Mr of 40 kD and a pI of 5.6 in CICs from the untreated HD patients. Congruent peptide maps of this component and its decreased amounts in CICs from sera of patients in remission suggests its quantitative involvement in the disease.

Antigen-Antibody Complex↗

PubMed1989

Regulation of rat growth hormone receptor gene expression.

A cDNA encoding the growth hormone (GH) receptor was cloned from rat liver. Both the nucleotide and translated amino acid sequence share greater than 70% similarity with the GH receptors from rabbit and human. An RNA probe was generated from this sequence for use in a solution hybridization assay to quantitate GH receptor mRNA expression in rat tissues. Expression was detected in 9/12 tissues examined, with the highest levels observed in the liver. Expression in liver, kidney, heart and muscle was developmentally regulated, being low at birth and rising to adult levels in 5 weeks. No difference was observed between hepatic expression in males and females, although livers from pregnant rats had elevated levels. Hypophysectomy and GH treatment did not affect hepatic GH receptor mRNA levels.

Aging↗

PubMed1989

The expression of prothymosin alpha gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation.

We isolated the cDNA for human prothymosin alpha (ProT alpha) from a human peripheral T-cell library using two synthetic oligonucleotides as probes. Hybridization studies with this cDNA showed that the ProT alpha mRNA is detectable in all the rat tissues studied but is most abundant in thymus and within this gland mainly synthesized by thymocytes. In the T-cell lineage, its expression is higher in proliferative immature thymocytes than in pre- and post-thymic T lymphocytes. A quite similar pattern was obtained with the proliferation-related protein proliferating cell nuclear antigen/cyclin. These data show that ProT alpha mRNA levels change with the maturation stage of T-cells. Moreover, the amount of ProT alpha transcript is increased in lymphocytes from human patients with leukemias. Our findings indicate a role for ProT alpha linked to lymphocyte proliferation.

Amino Acid Sequence↗

PubMed1988

A deletion mutation in the ApoC-II gene (ApoC-II Nijmegen) of a patient with a deficiency of apolipoprotein C-II.

The apolipoprotein C-II gene from a patient with a deficiency of apoC-II was cloned and sequenced. A single base deletion of a guanosine at position 2943 in exon three of the gene of the proband was identified by sequence analysis. This point mutation results in a shift of the reading frame and introduces a premature termination codon (TGA) at a position in the gene immediately following amino acid 17 of the mature C-II apolipoprotein. This single base deletion results in the loss of a normally occurring HphI restriction enzyme site in the apoC-II gene. Amplification of the mutant DNA sequence by the polymerase chain reaction and restriction enzyme digestion with HphI established that the patient is a homozygote for the base deletion. No apoC-II was detectable in the patient's plasma by two-dimensional gel electrophoresis and immunoblotting. We propose that the guanosine deletion is the primary genetic defect in this kindred leading to premature termination and formation of a nonfunctional truncated 17-amino acid C-II apolipoprotein which ultimately results in apoC-II deficiency.

Apolipoprotein C-II↗

PubMed1988

Diminished synthesis of catalase due to the decrease in catalase mRNA in Japanese-type acatalasemia.

In order to characterize the genetic defect in Japanese-type acatalasemia, we examined catalase synthesis in the cultured fibroblasts isolated from a patient suffering from this disease. The transcript of the mutant catalase gene was also analyzed by Northern blotting. It was demonstrated that the severe reduction in catalase protein in the acatalasemic patient is due to the defective synthesis of the enzyme caused by the lack of catalase mRNA. Using Southern blotting, we did not detect large deletion, insertion or rearrangement in the mutant catalase gene as compared with the normal one. We conclude that Japanese-type acatalasemia in this study is resulted by a small mutation in the non-coding region of catalase gene which affects some step in the catalase mRNA metabolism.

Acatalasia↗

PubMed1988

A novel method for producing anti-peptide antibodies. Production of site-specific antibodies to the T cell antigen receptor beta-chain.

Peptide antigens used to generate site-specific antibodies to proteins are of interest in the development of vaccines. The need to conjugate them to a carrier protein for optimal immunogenicity results in a number of problems including a possible immune response to the carrier. Here we describe a new method of synthesizing an immunogenic peptide antigen, referred to as multiple antigenic peptide (MAP), which may render the need for a carrier protein obsolete. A 14-residue sequence derived from the human T cell antigen receptor beta-chain constant region was selected, and the peptide was synthesized directly onto a branching lysine core with 8 copies of the 14-residue peptide linked to the core by the COOH-terminal amino acid. The molecular weight of this structure was 13,422 of which only 7% represents the lysine residues of the core. The octameric MAP was highly immunogenic in mice and rabbits, allowing production of polyclonal and monoclonal antibodies. The majority of these antibodies reacted with the peptide in its monomeric form as well as its octameric form. Moreover, the antibodies reacted with the intact beta-chain protein. The antigenic determinants of the peptide that were recognized by the antibodies included continuous determinants and conformational determinants. The NH2-terminal residues of the octameric MAP appeared to be most immunogenic. There were no antibodies to the central lysine core. This method of direct synthesis of a polymeric peptide provides accurate knowledge of the conformation and quantity of the peptide prior to immunization, which is usually not the case when peptides are conjugated to carriers. The method is versatile because the possibility exists to synthesize MAP with 16 or 32 peptide arms or to synthesize polymers containing two different peptides.

Amino Acid Sequence↗

PubMed1995

Different angiogenic pathways characterize superficial and invasive bladder cancer.

We have investigated by RNase protection analysis the expression of 2 angiogenic factors in 45 primary bladder tumors and 8 normal bladders. Expression of vascular endothelial growth factor (VEGF) was 3-fold higher and that of platelet-derived endothelial cell growth factor was 40-fold higher in tumors compared to normal bladder. However, the factors were differentially expressed in different stages of the cancer. Expression of VEGF in superficial tumors was 4-fold higher than in invasive tumors and 10-fold higher than in normal bladder (superficial versus invasive, P < 0.0006; superficial versus normal, P < 0.0002). Expression of platelet-derived endothelial cell growth factor in invasive tumors was 33-fold higher than in superficial tumors and 260-fold higher than in normal bladder (invasive versus superficial, P < 0.0001; invasive versus normal, P < 0.0003). In well differentiated or moderately differentiated superficial tumors which had invaded the lamina propria (pT1G1/2) VEGF expression was 4-fold higher in tumors which subsequently recurred at 3 months compared to those which did not recur (P < 0.002). Thus there are two distinct angiogenic pathways involved in different stages of bladder cancer, which is in keeping with the evidence for two different genetic pathways. Elevated VEGF expression predicts early recurrence of pT1G1/2 tumors.

Antisense Elements (Genetics)↗

PubMed1995

Identification of an enhancer responsible for tumor marker gene expression by means of transgenic rats.

The glutathione transferase P (GST-P) gene is known for its specific expression during chemical hepatocarcinogenesis of the rat and is used as a tumor marker for hepatocellular carcinoma. We have shown recently that the upstream 2.9-kb region of the GST-P gene is sufficient for conferring tumor-specific expression of the gene in vivo (S. Morimura et al., Proc. Natl. Acad. Sci. USA, 90: 2065-2068, 1993). To further identify crucial sequence elements regulating the unique expression of this gene, we have established six independent lines of transgenic rats bearing distinct areas of the GST-P gene that are connected to the chloramphenicol acetyltransferase coding region and analyzed changes of the chloramphenicol acetyltransferase activity during the course of chemical hepatocarcinogenesis. We demonstrate here that the enhancer, glutathione transferase P enhancer I, that is located 2.5 kb upstream of the GST-P gene is required and sufficient for its tumor-specific expression of the gene among other controlling elements. This approach to transgene expression could be used to define other enhancers, the activity of which is dependent on cellular changes such as carcinogenesis, development, and differentiation.

Animals↗