High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene

1989 ◽  
Vol 9 (9) ◽  
pp. 3982-3991
Author(s):  
A Lavigueur ◽  
V Maltby ◽  
D Mock ◽  
J Rossant ◽  
T Pawson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Malignant Transformation ◽  
P53 Protein ◽  
P53 Gene ◽  
Cell Types ◽  
Molecular Events ◽  
High Incidence ◽  
Transgenic Lines ◽  
Functional Inactivation

We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteosarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans.

scholarly journals High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene.

1989 ◽  
Vol 9 (9) ◽  
pp. 3982-3991 ◽  
Author(s):  
A Lavigueur ◽  
V Maltby ◽  
D Mock ◽  
J Rossant ◽  
T Pawson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Malignant Transformation ◽  
P53 Protein ◽  
P53 Gene ◽  
Cell Types ◽  
Molecular Events ◽  
High Incidence ◽  
Transgenic Lines ◽  
Functional Inactivation

We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteosarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans.

Beta-MHC and SMLC1 transgene induction in overloaded skeletal muscle of transgenic mice

1996 ◽  
Vol 270 (4) ◽  
pp. C1111-C1121 ◽  
Author(s):  
J. L. Wiedenman ◽  
I. Rivera-Rivera ◽  
D. Vyas ◽  
G. Tsika ◽  
L. Gao ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Troponin C ◽  
Type I ◽  
Initial Attempt ◽  
Specific Expression ◽  
Slow Type ◽  
Transgenic Lines ◽  
Fast Twitch Muscle ◽  
Mechanical Overload

The hypertrophic responses of white fast-twitch muscle to mechanical overload has been investigated using transgenic mice. After 7 wk of overload, endogenous beta-myosin heavy chain (MHC) and slow myosin light chain 1 and 2 (SMLC1, SMLC2) protein were increased in the overloaded plantaris (OP) muscle compared with sham-operated control plantaris (CP)muscle. Concurrently, the levels of endogenous beta-MHC, SMLC1, SMLC2, and cardiac/slow troponin C (CTnC) mRNA transcripts were significantly increased in OP muscles, whereas skeletal troponin C (sTnC) mRNA transcript levels decreased. As an initial attempt to locate DNA sequence(s) that governs beta-MHC induction in response to mechanical overload, multiple independent transgenic lines harboring four different human beta-MHC transgenes (beta 1286, beta 988, beta 450, beta 141) were generated. Except for transgene beta 141, muscle-specific expression and induction (3- to 22-fold) in OP muscles were observed by measuring chloramphenicol acetyltransferase activity (CAT assay). Induction of a SMLC1 transgene (3920SMLC1) in OP muscles was also observed. Collectively, these in vivo data provide evidence that 1) a mechanical overload inducible element(s) is located between nucleotides -450 and +120 of the human beta-MHC transgene, 2) 3,900 bp of 5' sequence is sufficient to confer mechanical overload induction of a SMLC1 transgene, and 3) the increased expression of slow/type I isomyosin (beta-MHC, SMLC1, SMLC2) in response to mechanical overload is regulated, in part, transcriptionally.

Cellular Dynamics during Spinal Cord Regeneration in Larval Zebrafish

2019 ◽  
Vol 41 (1-2) ◽  
pp. 112-122 ◽  
Author(s):  
Consuelo Anguita-Salinas ◽  
Mario Sánchez ◽  
Rodrigo A. Morales ◽  
María Laura Ceci ◽  
Diego Rojas-Benítez ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Immune Cells ◽  
Cell Types ◽  
Regenerative Process ◽  
Spinal Cord Regeneration ◽  
Cord Injury ◽  
Complete Reversal ◽  
Transgenic Lines ◽  
Functional Regeneration

The study of spinal cord regeneration using diverse animal models, which range from null to robust regenerative capabilities, is imperative for understanding how regeneration evolved and, eventually, to treat spinal cord injury and paralysis in humans. In this study, we used electroablation to fully transect the spinal cord of zebrafish larvae (3 days postfertilization) and examined regeneration of the tissue over time. We used transgenic lines to follow immune cells, oligodendrocytes, and neurons in vivo during the entire regenerative process. We observed that immune cells are recruited to the injury site, oligodendrocytes progenitor cells (olig2-expressing cells) invade, and axons cross the gap generated upon damage from anterior to reinnervate caudal structures. Together with the recovery of cell types and structures, a complete reversal of paralysis was observed in the lesioned larvae indicating functional regeneration. Finally, using transplantation to obtain mosaic larvae with single-labeled neurons, we show that severed spinal axons exhibited varying regenerative capabilities and plasticity depending on their original dorsoventral position in the spinal cord.

Transgenic Expression of Bach1 Transcription Factor Results in Down-Regulation of the p45 Target Genes in Megakaryocytic Lineage Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1605-1605 ◽  
Author(s):  
Tsutomu Toki ◽  
Fumiki Katsuoka ◽  
Rika Kanezaki ◽  
Seiji Watanabe ◽  
Takuya Kamio ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Target Genes ◽  
Fetal Liver ◽  
Regulatory Element ◽  
Mutant Mice ◽  
Transgenic Expression ◽  
Transgenic Lines ◽  
Recognition Elements ◽  
Null Mutant Mice

Abstract Both p45 and BACH transcription factors can form dimers with one of the small Maf proteins, and these heterodimers bind to Maf recognition elements (MARE). MARE is known to act as a critical cis-regulatory element of erythroid and megakaryocytic genes. While detailed analyses of p45 -null mutant mice and small maf compound mutant mice revealed that these factors are both critical for platelet production, the functional contributions of BACH1 and the relationship or redundancy between BACH1 and p45 in megakaryocytes remain to be clarified. To address these issues, we generated transgenic lines of mice bearing human BACH1 cDNA under the control of the GATA-1 locus hematopoietic regulatory domain. The transgenic mouse lines showed significant thrombocytopenia associated with impaired maturation of the megakaryocytes, and they developed myelofibrosis. The megakaryocytes overexpressing the BACH1 transgene exhibited reduced proplatelet formation. Since the phenotype of the BACH1 transgenic mice resembled that of the p45 -deficient mice, we examined the expression of the p45 NF-E2 target genes in the primary megakaryocytes from fetal liver cells of the BACH1 transgenic mice. RT-PCR analyses showed that expression of the hematopoietic-specific ß1-tubulin, thromboxane synthase ( TXAS), and of the 3ß-hydroxy-steroid dehydrogenase genes was significantly downregulated in the megakaryocytes from BACH1 transgenic mice. The TXAS gene is a well-known MARE-dependent gene containing functional MAREs in its promoter and in the second intron. To ask whether BACH1 actually binds to MARE in the megakaryocytic genes, we then performed chromatin immunoprecipitation (ChIP) analysis with a BACH1-specific antibody. A ChIP assay with a human megakaryocytic cell line, UT-7/TPO, demonstrated that BACH1 bound to the promoter and enhancers region in vivo. As expected, co-transfection with BACH1 or Bach1-MafK fusion protein (B1K) expression plasmids repressed the reporter gene activity driven by the TXAS promoter. These findings thus provide evidence that BACH1 acts as a transcriptional repressor in the regulation of MARE-dependent genes in megakaryocytes.

Hyperactivable NFAT1 Ameliorates Autoimmune Encephalitis In Vivo.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 711-711
Author(s):  
Srimoyee Ghosh ◽  
Sergei B Koralov ◽  
Irena Stevanovic ◽  
Mark S Sundrud ◽  
Yoshiteru Sasaki ◽  
...  
Keyword(s):  
T Cells ◽  
Transgenic Mice ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Autoimmune Encephalitis ◽  
Cell Types ◽  
Wild Type ◽  
Ifn Γ

Abstract Abstract 711 Naïve CD4 T cells differentiate into diverse effector and regulatory subsets to coordinate the adaptive immune response. TH1 and TH2 effector subsets produce IFN-γ and IL-4, respectively, whereas proinflammatory TH17 cells are key regulators of autoimmune inflammation, characteristically produce IL-17 and IL-22 and differentiate in the presence of inflammatory cytokines like IL-6 and IL-21 together with TGF-β. Naive T cells can also differentiate into tissue-protective induced T regulatory (iTreg) cells. NFAT proteins are highly phosphorylated and reside in the cytoplasm of resting cells. Upon dephosphorylation by the Ca2+/calmodulin-dependent serine phosphatase calcineurin, NFAT proteins translocate to the nucleus, where they orchestrate developmental and activation programs in diverse cell types. In this study, we investigated the role of the Ca/NFAT signaling pathway in regulating T cell differentiation and the development of autoimmune diseases. We generated transgenic mice conditionally expressing a hyperactivable version of NFAT1 (AV-NFAT1) from the ROSA26 locus. To restrict AV-NFAT1 expression to the T cell compartment, ROSA26-AV-NFAT1 transgenic mice were bred to CD4-Cre transgenic mice. Naïve CD4 T cells freshly isolated from AV mice produced significantly less IL-2 but increased amounts of the inhibitory cytokine IL-10. To investigate the role of NFAT1 in the generation of TH1, TH2, Tregand TH17 cells, the respective cell types were generated from CD4 T cells of AV mice by in vitro differentiation. T cells from AV-NFAT1 mice exhibited a dysregulation of cytokine expression, producing more IFN-γ and less IL-4. While the numbers of CD4+CD25+ “natural” Treg cells in peripheral lymphoid organs and their in vitro suppressive functions were slightly decreased in AV mice, iTreg generation from CD4+CD25- T cells of AV mice as compared to wild type cells was markedly enhanced. Moreover, TH17 cells generated in vitro from CD4 T cells of AV mice in the presence of IL-6, IL-21 and TGF-β exhibited dramatically increased expression of both IL-10 and IL-17 as compared to wild type controls. To investigate putative NFAT binding sites in the IL-10 and IL-17 gene loci, we performed chromatin immunoprecipitation experiments. We show that NFAT1 can bind at the IL-17 locus at 3 out of 9 CNS regions which are accessible specifically during TH17 but not during TH1 and TH2 differentiation. Furthermore, we provide evidence that NFAT1 binds one CNS region in the IL10-locus in TH17 cells. To verify our observations in vivo, we induced experimental autoimmune encephalitis (EAE) in AV mice and wild type controls with the immunodominant myelin antigen MOG33-55 emulsified in complete Freund‘s adjuvant. While wild type animals showed a normal course of disease with development of tail and hind limb paralysis after approximately 10 days, AV mice showed a markedly weaker disease phenotype with less severe degrees of paralysis and accelerated kinetics of remission. Moreover at the peak of the response, there were fewer CD4+CD25- but more CD4+CD25+ T cells in the CNS of AV animals compared to wild type controls. Surprisingly, these cells produced significantly more IL-2, IL-17 and IFN-γ upon restimulation, even though they displayed decreased disease. In summary, our data provide strong evidence that NFAT1 contributes to the regulation of IL-10 and IL-17 expression in TH17 cells and show that increasing NFAT1 activity can ameliorate autoimmune encephalitis. This could occur in part through upregulation of IL-10 expression as observed in vitro, but is also likely to reflect increased infiltration of regulatory T cells into the CNS as well as increased conversion of conventional T cells into Foxp3+ regulatory T cells within the CNS. Disclosures: No relevant conflicts of interest to declare.

Persistent Human γ-Globin Expression in Adult Transgenic Mice Following Selective Deletion of Two Repressor Elements Located 3′ to the Aγ-Globin Gene.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1585-1585
Author(s):  
Maria Gazouli ◽  
Elena Katsantoni ◽  
Theodore Kosteas ◽  
Nicholas P. Anagnou
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Globin Gene ◽  
Adult Life ◽  
Single Copy ◽  
Perinatal Period ◽  
Globin Genes ◽  
Cis Acting ◽  
Transgenic Lines

Abstract Adult β-globin gene expression is tightly regulated during development and hematopoiesis. The human globin genes undergoing two developmental switches are regulated by a complex interplay between cis-acting elements and stage-specific trans-acting factors. Understanding the molecular basis of globin gene switching is of particular interest as persistent expression of the fetal γ-globin genes in the adult ameliorates the effects of hemoglobinopathies. Natural occurring deletions within the human β-globin gene cluster lead to specific clinical syndromes characterized by increased production of fetal hemoglobin (HbF) in adult life. These clinical syndromes provide an excellent model to reveal and delineate novel cis-acting elements involved in the developmental control of hemoglobin switching. One major hypothesis, which accounts for these distinct phenotypic features, assumes that silencers located within the Aγ to δ gene region, are deleted in both HPFH and δβ-thalassemias leading to the failure of switching. Previous studies of our laboratory suggested that four elements (Enh, F, O and P) located within the Aγ toδ globin intergenic region, exhibited silencer activity in transient assays (Clin Res 41:308, 1993 and Blood 84:506, 1994) and that the Enh and F elements were capable of down-regulating transcription of the human β-globin locus in an embryonic-specific manner in transgenic mice (Exp Hematol 32:224, 2004). In the present study, we sought to further clarify the in vivo role of the Enh and F elements in the silencing of the fetal Aγ-gene. To this end, we have generated transgenic mice by using cosmid constructs containing the full length human globin LCR linked to the 3.3 kb Aγ gene, lacking both the Enh and F elements. As controls, we used transgenic lines containing the full length LCR linked to the 5.6 kb Aγ-gene construct, which includes both the Enh and F elements, previously shown by us (Blood102:3412, 2003) and others (Nature350:252, 1991) to be autonomously regulated during the perinatal period. Three transgenic lines for the LCR 3.3 kb Aγ-gene construct have been generated. Cosmid integrity and copy numbers (2, 3 and 4 copies respectively) were determined by Southern blot analysis. Expression analysis in adult blood RNA performed by S1 nuclease protection and real-time reverse transcriptase PCR, documented persistence of expression of Aγ-gene in adult life. To further investigate whether the persistence of Aγ-gene expression was not a non-specific effect of the multicopy integrants, we generated a new series of single copy mice by cross-breeding the three transgenic lines with a line expressing the Cre recombinase gene (CAG-Cre). As expected, in the control LCR-5.6 kb Aγ lines, containing the Enh and F elements, the Aγ-globin gene was silenced in all lines tested in the adult stage. In contrast, high levels of Aγ-globin gene expression, similar to those of multicopy integrants were documented in all three generated single copy LCR-3.3 kb Aγ lines, lacking the Enh and F elements. Thus, this study documents directly for the first time the in vivo role of of these two gene-proximal negative regulatory elements on the silencing of the Aγ-gene in the perinatal period and may permit the design of future therapeutic strategies for their exploitation in therapeutic approaches for thalassemias.

scholarly journals Differential regulation of the N-myc gene in transfected cells and transgenic mice.

1990 ◽  
Vol 10 (5) ◽  
pp. 2096-2103 ◽  
Author(s):  
K Zimmerman ◽  
E Legouy ◽  
V Stewart ◽  
R Depinho ◽  
F W Alt
Keyword(s):  
Transgenic Mice ◽  
Developmental Stages ◽  
Specific Expression ◽  
Endogenous Gene ◽  
Numerous Cell ◽  
Transgenic Lines ◽  
Myc Gene ◽  
Early Developmental

The N-myc gene is expressed specifically in the early developmental stages of numerous cell lineages. To assay for sequences that could potentially regulate N-myc expression, we transfected constructs that contained murine N-myc genomic sequences linked to a reporter gene and genomic clones that contained the complete human or murine N-myc genes into cell lines that either express or do not express the endogenous N-myc gene. Following either transient or stable transfection, the introduced N-myc sequences were expressed regardless of the expression status of the endogenous gene. In contrast, when the clones containing the complete human N-myc gene were introduced into the germline of transgenic mice, expression in some transgenic lines paralleled the tissue- and stage-specific expression of the endogenous murine gene. These findings demonstrate differences in the regulation of N-myc genes in recipient cells following in vitro versus in vivo introduction, suggesting that early developmental events may play a role in the regulation of N-myc expression.

scholarly journals Expression of Interleukin 9 in the Lungs of  Transgenic Mice Causes Airway Inflammation, Mast Cell Hyperplasia, and Bronchial Hyperresponsiveness

1998 ◽  
Vol 188 (7) ◽  
pp. 1307-1320 ◽  
Author(s):  
Ulla-Angela Temann ◽  
Gregory P. Geba ◽  
John A. Rankin ◽  
Richard A. Flavell
Keyword(s):  
Transgenic Mice ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Bronchial Hyperresponsiveness ◽  
Cell Types ◽  
Clara Cell ◽  
Cell Hyperplasia ◽  
Wide Range ◽  
Interleukin 9

Interleukin (IL)-9, a pleiotropic cytokine produced by the Th2 subset of T lymphocytes has been proposed as product of a candidate gene responsible for asthma. Its wide range of biological functions on many cell types involved in the allergic immune response suggests a potentially important role in the complex pathogenesis of asthma. To investigate the contributions of IL-9 to airway inflammation and airway hyperresponsiveness in vivo, we created transgenic mice in which expression of the murine IL-9 cDNA was regulated by the rat Clara cell 10 protein promoter. Lung selective expression of IL-9 caused massive airway inflammation with eosinophils and lymphocytes as predominant infiltrating cell types. A striking finding was the presence of increased numbers of mast cells within the airway epithelium of IL-9–expressing mice. Other impressive pathologic changes in the airways were epithelial cell hypertrophy associated with accumulation of mucus-like material within nonciliated cells and increased subepithelial deposition of collagen. Physiologic evaluation of IL-9–expressing mice demonstrated normal baseline airway resistance and markedly increased airway hyperresponsiveness to inhaled methacholine. These findings strongly support an important role for IL-9 in the pathogenesis of asthma.

scholarly journals A Mutant of Human Papillomavirus Type 16 E6 Deficient in Binding α-Helix Partners Displays Reduced Oncogenic Potential In Vivo

2002 ◽  
Vol 76 (24) ◽  
pp. 13039-13048 ◽  
Author(s):  
Marie Nguyen ◽  
Shiyu Song ◽  
Amy Liem ◽  
Elliot Androphy ◽  
Yun Liu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
P53 Protein ◽  
Human Papillomaviruses ◽  
Skin Tumors ◽  
Cellular Proteins ◽  
Viral Gene ◽  
Gene Encoding ◽  
Tumor Viruses ◽  
Α Helix

ABSTRACT Human papillomaviruses (HPVs) are small DNA tumor viruses that are the causative agent of warts and are associated with many anogenital cancers. The viral gene encoding the E6 protein has been found to be involved in HPV oncogenesis. E6 is known to inactivate the cellular tumor suppressor, p53. In addition, E6 has been shown to bind to a variety of other cellular proteins. The focus of this study was to determine what role the interactions of E6 with a subset of cellular proteins which contain a common α-helical domain in their E6 binding region (α-helix partners) play in E6-mediated phenotypes. We generated transgenic mice expressing a mutant of E6, E6I128T, which is defective for binding at least a subset of the α-helix partners, including E6AP, the ubiquitin ligase that mediates E6-dependent degradation of the p53 protein, to determine whether binding of α-helix partners plays a role in E6-mediated activities in vivo. Unlike mice expressing the wild-type E6 (strain K14E6WT), the mice expressing E6I128T lacked the ability to alter the radiation-induced block to DNA synthesis and promote the formation of benign skin tumors in conjunction with chemical carcinogens. Additionally, they displayed reduced levels of skin hyperplasia, spontaneous skin tumors, and tumor progression activity compared to those of the K14E6WT mice. From these results, we conclude that a domain in E6 that mediates α-helix partner binding is critical for E6-induced phenotypes in transgenic mice.

scholarly journals The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation

2015 ◽  
Vol 112 (32) ◽  
pp. 10002-10007 ◽  
Author(s):  
Liang Chen ◽  
Farooq Rashid ◽  
Abdullah Shah ◽  
Hassaan M. Awan ◽  
Mingming Wu ◽  
...  
Keyword(s):  
P53 Protein ◽  
P53 Gene ◽  
P53 Mutation ◽  
Single Amino Acid ◽  
Human Lung Cancer ◽  
Rna Aptamer ◽  
Wild Type ◽  
Wild Type P53

p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers are short single-stranded oligonucleotides that are able to bind various targets, and they are typically isolated from an experimental procedure called systematic evolution of ligand exponential enrichment (SELEX). Using a previously unidentified strategy of contrast screening with SELEX, we have isolated an RNA aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in vivo assays. p53R175H-APT decreased the growth rate, weakened the migration capability, and triggered apoptosis in human lung cancer cells harboring p53R175H. Further analysis actually indicated that p53R175H-APT might partially rescue or correct the p53R175H to function more like the wild-type p53. In situ injections of p53R175H-APT to the tumor xenografts confirmed the effects of this RNA aptamer on p53R175H mutation in mice.

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