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At least 721 records · Page 40Linked to original sources
PubMed2000

Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a].

In this study, we created LDL receptor (LDLr) defective (WHHL) transgenic rabbits expressing human apo[a] to examine whether LDLr mediates the Lp[a] clearance from the plasma. By crossbreeding WHHL rabbits with human apo[a] transgenic rabbits, we obtained two groups of human apo[a] transgenic rabbits with defective LDLr functions: apo[a](1/0) WHHL heterozygous (LDLr(+/-) and apo[a](+/0) WHHL homozygous (LDLr(-/-) rabbits. The lipid and lipoprotein levels of human apo[a] WHHL rabbits were compared to those of human apo[a] transgenic rabbits with normal LDLr functions (LDLr(+/+). The apo[a] production rate was evaluated by analyzing apo[a] mRNA expression in the liver, the major site for apo[a] synthesis in transgenic rabbits. We found that pre-beta lipoproteins were markedly increased accompanied by a 2-fold increase in the plasma Lp[a] in apo[a](+/0)/LDLr(+/-) rabbits and a 4.2-fold increase in apo[a](+/0)/LDLr(-/-) rabbits compared with that in apo[a](+/0) rabbits with normal LDLr function. In apo[a](+/0)/LDLr(-/-) rabbits, there was a marked increase in plasma total cholesterol and triglycerides, as was found in their counterpart non-transgenic WHHL rabbits. Northern blot analysis revealed that hepatic apo[a] expression in WHHL transgenic rabbits was similar to that in LDLr(+/+) transgenic rabbits, suggesting the accumulation of plasma Lp[a] in WHHL transgenic rabbits was not due to increased apo[a] synthesis. In conclusion, absence of a functional LDLr leads to a marked accumulation of plasma Lp[a] in human apo[a] transgenic WHHL rabbits and LDLr may participate in the catabolism of Lp[a] in rabbits.

Animals↗
PubMed2002

Growth and differentiation of transgenic callus regulated by phytohormones and antibiotics in transformation of loblolly pine.

Mature zygotic embryos of loblolly pine (Pinus taeda L.) were transformed by Agrobacterium tumefaciens strain LBA 4404 harbouring the plasmid pBI121 which carried the selectable marker gene, neomycin phosphotransferase II (npt II) controlled by the promoter of the nopaline synthase gene, and the uidA reporter gene, encoding beta-glucuronidase (GUS) driven by the cauliflower mosaic virus 35S promoter. Organogenic transgenic calli and transgenic regenerated plantlets were produced on selection medium containing 15 mg/L kanamycin, and confirmed by GUS histochemical staining, polymerase chain reaction (PCR), and southern blot analysis. Influences of phytohormone (BA/IBA) and antibiotics on growth and differentiation of organogenic transgenic calli were investigated. Of the phytohormone (BA/IBA) and antibiotics administered, 500 mg/L carbenicillin combined with 2 mg/L BA and 0.5 mg/L IBA (BA/IBA = 4) resulted in a 54.2% higher increase in the growth of transgenic calli as well as in the differentiation of transgenic calli, which was 45.7% more than that of control on the 6th week of culture. Claforan at 500 mg/L combined with 2 mg/L BA and 0.5 mg/L IBA resulted in a 40.8% increase in the growth of transgenic calli, and 38.7% increase in the frequency of transgenic calli forming adventitious shoots compared with the control. The growth and differentiation of transgenic calli of loblolly pine was reduced preferentially by higher BA/IBA (BA/IBA = 8), as well as high concentration of antibiotics (carbenicillin and claforan, 550 mg/L each). But it was observed that 450 mg/L and 500 mg/L carbenicillin and claforan caused an increase in growth and differentiation of transgenic calli. These results suggested that the establishment of an efficient Agrobacterium tumefaciens-mediated transformation protocol for stable integration of foreign genes into loblolly pine was also dependent on the regulation of phytohormone and antibiotic on growth and differentiation of transgenic calli. This work could be useful for the future studies of genetic transformation of conifers.

Anti-Bacterial Agents↗
PubMed2002

[Studies on the distorted segregation of foreign genes in transgenic rice progenies].

The segregation mode of transgenes was investigated in the transgenic progenies of three rice varieties (lines) produced by Agrobacterium-mediated transformation. The transgenic lines all contained the Bacillus thuringiensis cry1Ab gene, under the control of a maize ubiquitin promoter, and linked in tandem with gusA and hpt genes. PCR analysis showed the transgenes cry1Ab and gusA co-segregated in all self and crossed progenies tested. Therefore, GUS bio-assay of leaf or endosperm tissues was used to monitor transgene segregation in the experiment. It was found that the ratio of positive to negative plants was significantly smaller than 3:1 in all heterozygous plants derived progenies, which implied the segregation biased from typical Mendelian mode for a single dominant gene. Less GUS positive plants, and consequently less homozygous transgenic lines than expected were recovered from the self progenies. Transgenic heterozygous plants (+/-) were crossed as female or male parent to conventional rice varieties (-/-), and the ratio of gusA positive (+/-) to negative (-/-) plants was investigated in test F1 population. When used as female parent, the segregation fit to 1:1, but significantly smaller than 1:1 when used as male parent. The seed-set of transgenic Nipponbare progeny was investigated individually for GUS positive and negative plants. It was found that the positive plants had an average seed-set of 64.5%, significantly lower than that of negative plants (77.9%). The biological and genetic basis of distorted segregation of transgenes was discussed and deduced on the basis of above results, and the authors are inclined to ascribe these phenomena to the poor competitive ability of pollens carrying transgenes.

Bacillus thuringiensis Toxins↗
PubMed2004

[Endosperm-specific expression of the ferritin gene in transgenic rice (Oryza sativa L.) results in increased iron content of milling rice].

Iron deficiency is the most widespread micronutrient deficiency world-wild, and is estimated to affect about 30% of the world population. To increase the iron content of rice in Chinese, the 764 bp cDNA of ferritin gene was cloned from soybean (Phaseolus limensis), and constructed between the 1 353 bp rice glutelin GluB-1 promoter and NOS terminator in a binary vector pCAMIBA1301. The constructed pYF1067 vector was introduced into Agrobacterium strain EHA105, and used for transformation of the primary callus derived from immature embryos of a high-yielding rice ( Oryza sativa L. ssp. japonica) variety Wuxiangjin 9. Under the selection on hygromycin-containing medium, seventeen independent transgenic rice lines, total more than 80 transgenic plants, were finally regenerated, and most of these transgenic rice plants grew normally. PCR and Southern blot analysis of total DNA from primary transformants confirmed that one to three copies of the transgenes integrated into the genome of most of the transgenic plants, and they could be stably transmitted into the progeny of the transgenic rice. Northern blot analysis showed that the ferritin gene could specifically express in the endosperm of transgenic rice with high level, while no or low expression in leaves. The expression level varied among different independent transgenic rice plants. There was a significant effect of the high-expression of ferritin on the increased iron content in transgenic rice, the iron content in the milling rice of transgenic rice was up to 64% higher than that of the untransformed wild-type plant, whereas no significant alteration of the zinc level occurred between these two type rice plants.

Ferritins↗
PubMed1994

Transgenic hepatocarcinogenesis in the rat.

Although transgenic hepatocarcinogenesis has been accomplished in the mouse with a number of genetic constructs targeting the oncogene to expression primarily in the liver, no example of this process has yet been developed in the rat. Because our understanding of the multistage nature of hepatocarcinogenesis is most advanced in the rat, we have developed a strain of transgenic rats carrying the promoter-enhancer sequences of the mouse albumin gene linked 5' to the simian virus-40 T antigen gene. A line of transgenic rats bearing this transgene has been developed from a single founder female. Five to six copies of the transgene, possibly in tandem, occur within the genome of the transgenic animals, which are maintained by heterozygous matings. Livers of transgenic animals are histologically normal after weaning; at 2 months of age, small foci of vacuolated cells appear in this organ. By 4 months of age, all animals exhibit focal lesions and nodules consisting primarily of small basophilic cells, many of which exhibit considerable cytoplasmic vacuolization. Mating of animals each bearing the transgene results in rats with a demyelinating condition that develops acutely in pregnant females and more chronically in males. Ultrastructural studies of these cells indicate that the vacuoles contain substantial amounts of glycogen, with the cells resembling hepatoblasts. Malignant neoplasms with both a glandular and a hepatoblastoma/hepatocellular carcinoma pattern arise from the nodules. Enzyme and immunohistochemical studies of all lesions reveal many similarities in gene expression to comparable lesions in rats subjected to chemically induced hepatocarcinogenesis, with certain exceptions. The placental form of glutathione-S-transferase is absent from all lesions in the transgenic animal, as is the expression of connexin 32. A significant number of lesions express serum albumin, and many, but not all, exhibit the T antigen. Lesions expressing the T antigen also contain stainable amounts of the p53 gene product; by contrast, normal hepatocytes express only very low levels of the T antigen within their nuclei and no demonstrable p53. All of the animals develop hepatic lesions, and approximately one-third also develop adenomas and carcinomas derived from the islet cells of the pancreas. Although there are differences in the morphology, biology, and genetic expression in early and late hepatic lesions in this strain of transgenic rat, many similarities also occur, making this a potential model system with which to study the interactions of environmental factors with a genetic program for hepatocarcinogenesis.

Animals↗
PubMed1996

Growth enhancement in transgenic tilapia by ectopic expression of tilapia growth hormone.

The generation of transgenic fish with the transfer of growth hormone (GH) genes has opened new possibilities for the manipulation of growth in economically important fish species. The tilapia growth hormone (tiGH) cDNA was linked to the human cytomegalovirus (CMV) enhancer-promoter and used to generate transgenic tilapia by microinjection into one-cell embryos. Five transgenic tilapia were obtained from 40 injected embryos. A transgenic animal containing one copy of the transgene per cell was selected to establish a transgenic line. The transgene was stably transmitted to F1 and F2 generations in a Mendelian fashion. Ectopic, low-level expression of tiGH was detected in gonad and muscle cells of F1 transgenic tilapia by immunohystochemical analysis of tissue sections. Nine-month-old transgenic F1 progeny were 82% larger than nontransgenic fish at p = .001. These results showed that low-level ectopic expression of tiGH resulted in a growth acceleration in transgenic tilapia. Tilapia GH gene transfer is an alternative for growth acceleration in tilapia.

Animals↗
PubMed1999

DNA methylation pattern of a tandemly repeated LacZ transgene indicates that most copies are silent.

The Pgk-1,2-lacZ transgene consists of the ubiquitously-expressed Pgk-1 promoter driving expression of the E. coli lacZ reporter gene. We studied the expression of this transgene in a mouse strain carrying 8-9 tandem copies of this construct. When inherited through the male germ line, the transgene was expressed in all tissues examined but when inherited through the female germ line, the transgene became irreversibly inactivated. The lacZ region is a CpG-rich island that was essentially entirely methylated in all copies of the silent, maternally-inherited transgene. At the active transgenic locus, all but one of the copies were entirely methylated. This one unmethylated copy was adjacent to the cellular DNA and was presumed to be the expressed transgene copy. These results suggest that the tandem repeats of transgenes become silenced by a mechanism associated with DNAmethylation and that proximity to the cellular genome may be important in maintaining expression against the spread of inactivation from the adjacent silent transgenes.

Animals↗
PubMed2001

Integration of a c-myc transgene results in disruption of the mouse Gtf2ird1 gene, the homologue of the human GTF2IRD1 gene hemizygously deleted in Williams-Beuren syndrome.

Transgenic mice expressing c-myc under the control of the albumin promoter and enhancer develop liver tumors and have served as a useful model for studying the progression of hepatocarcinogenesis. The chromosomes of one line of c-myc transgenic mice carry the reciprocal translocation t(5;6)(G1;F2) adjacent to the transgene insertion site on the 5G1-ter segment translocated to chromosome 6. To characterize the genomic alterations in the c-myc transgenic animals, we have cloned the mouse DNA flanking the transgene array. By linkage mapping, the transgene integration site was localized to the region of distal chromosome 5 syntenic to the region on human chromosome 7q11.23 that is hemizgygously deleted in Williams-Beuren syndrome, a multisystemic developmental disorder. Comparison of the genomic DNA structure in wildtype and transgenic mice revealed that the transgene integration had induced an approximately 40-kb deletion, starting downstream of the Cyln2 gene and including the first exon of the Gtf2ird1 gene. Gtf2ird1 encodes a polypeptide related to general transcription factor TFII-I, and it is the mouse orthologue of GTF2IRD1 (WBSCR11), one of the genes commonly deleted in Williams-Beuren syndrome patients. Loss of the 5' end of the Gtf2ird1 gene resulted in greatly reduced expression of Gtf2ird1 mRNA in mice homozygous for the transgene.

Animals↗
PubMed2002

FISH analysis of 142 EGFP transgene integration sites into the mouse genome.

Production of transgenic animals is an important technique for studying various biological processes. However, whether the integration of a particular transgene occurs randomly in the mouse genome has not been determined. Analysis by fluorescence in situ hybridization of the integration sites of the 142 EGFP (a mutant of green fluorescent protein) transgenic lines that we produced showed that the transgenes had become incorporated into every mouse chromosome. A single integration site was observed in 82.4% of the lines. The concomitant integrations of transgene into two different loci were observed in 15 cases (10.6%). In 3 cases, the transgenic founder mice showed chimerism in integration sites (2.1%). Chromosomal translocation was observed in 7 cases (4.9%). Moreover, when we statistically analyzed the transgene integration sites of these mouse lines, they were shown to distribute unevenly throughout the genome. This is the first report to analyze the transgene integration sites by producing more than 100 transgenic mouse lines.

Animals↗
PubMed2000

Decreased left ventricular ejection fraction in transgenic mice expressing mutant cardiac troponin T-Q(92), responsible for human hypertrophic cardiomyopathy.

The causality of mutant sarcomeric proteins in hypertrophic cardiomyopathy (HCM) is well established. The current emphasis is to elucidate the pathogenesis of HCM in transgenic animal models. We determined the left ventricular ejection fraction (LVEF) in transgenic mice expressing mutant cardiac troponin T (cTnT)-Q(92), known to cause HCM in humans. Transgenes were constructed by placing wild-type (R(92)) or mutant (Q(92)) full-length human cTnT cDNAs 3' into a 5.5-kb murine [alpha -myosin heavy chain (MyHC)] promoter injected into fertilized zygotes. Three wild-type and six mutant lines were produced. Transgene mRNA and proteins, detected using transgene-specific probes were expressed at high levels in all wild-type and three mutant lines. The total cTnT mRNA pool was increased by up to five-fold in transgenic mice, but the total cTnT protein remained unchanged. The mean values of LVEF, determined by(178)Ta radionuclide angiography, were 57.8+/-6% (n=4) in non-transgenic littermate (NLM), 53.3+/-10 (n=6) in wild-type and 39. 4+/-6 (n=5) in mutant transgenic mice (P=0.009). The heart/body weight ratios and the number of cells stained with terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling were similar among the groups. Three mutant mice had myocyte disarray and excess interstitial collagen and two had normal myocardial structure despite having reduced LVEF. Thus, in vivo expression of the mutant cTnT-Q(92)protein, responsible for human HCM, impaired global cardiac systolic function in transgenic mice, which also occurred in the absence of myocyte disarray and increased interstitial collagen.

Animals↗
PubMed2005

Transgene copy number-dependent rescue of murine beta-globin knockout mice carrying a 183 kb human beta-globin BAC genomic fragment.

We report the generation and characterisation of the first transgenic mice exclusively expressing normal human beta-globin ((hu)beta-globin) from a 183 kb genomic fragment. Four independent lines were generated, each containing 2-6 copies of the (hu)beta-globin locus at a single integration site. Steady state levels of (hu)beta-globin protein were dependent on transgene copy number, but independent of the site of integration. Hemizygosity for the transgene on a heterozygous knockout background ((hu)beta(+/0), (mu)beta(th-3/+)) complemented fully the hematological abnormalities associated with the heterozygous knockout mutation in all four lines. Importantly, the rescue of the embryonic lethal phenotype that is characteristic of homozygosity for the knockout mutation was also demonstrated in two transgenic lines that were homozygous for two copies of the (hu)beta-globin locus, and in one transgenic line, which was hemizygous for six copies of the (hu)beta-globin locus. Our results illustrate the importance of transgene copy number determination and of the hemizygosity/homozygosity status in phenotypic complementation studies of transgenic mice containing large heterologous transgenes. Transgenic mouse colonies with 100% (hu)beta-globin production from the intact (hu)beta-globin locus have been established and will be invaluable in comparative and gene therapy studies with mouse models containing specific beta-thalassemia mutations in the (hu)beta-globin locus.

Animals↗
PubMed2005

Cells of human aminopeptidase N (CD13) transgenic mice are infected by human coronavirus-229E in vitro, but not in vivo.

Aminopeptidase N, or CD13, is a receptor for serologically related coronaviruses of humans, pigs, and cats. A mouse line transgenic for the receptor of human coronavirus-229E (HCoV-229E) was created using human APN (hAPN) cDNA driven by a hAPN promoter. hAPN-transgenic mice expressed hAPN mRNA in the kidney, small intestine, liver, and lung. hAPN protein was specifically expressed on epithelial cells of the proximal convoluted renal tubules, bronchi, alveolar sacs, and intestinal villi. The hAPN expression pattern within transgenic mouse tissues matched that of mouse APN and was similar in mice heterozygous or homozygous for the transgene. Primary embryonic cells and bone marrow dendritic cells derived from hAPN-transgenic mice also expressed hAPN protein. Although hAPN-transgenic mice were resistant to HCoV-229E in vivo, primary embryonic cells and bone marrow dendritic cells were infected in vitro. hAPN-transgenic mice are valuable as a source of primary mouse cells expressing hAPN. This hAPN-transgenic line will also be used for crossbreeding experiments with other knockout, immune deficient, or transgenic mice to identify factors, in addition to hAPN, that are required for HCoV-229E infection.

Animals↗
PubMed1997

Overexpression of growth-associated proteins in the neurons of adult transgenic mice.

The Thy-1.2 expression cassette described in this report drives strong constitutive expression of transgenes specifically in the neurons of adult transgenic mice. Transgene expression begins at P6-10, at a time when it can affect activity-dependent rearrangements of synaptic connections and neuron-glia interactions during the late phases of nervous system development. Slightly earlier expression is detected in the developing cerebellum, where transgenes could also affect granule cell migration. Probably due to the strong genetic context sensitivity of the expression construct, expression patterns differ considerably among transgenic lines. Accordingly, neuron types can be subdivided into a group that consistently displays substantial expression in all tested transgenic lines, and in those where expression is founder-specific. About a fifth of the transgenic lines displayed quite generalized expression in neurons. These properties of the Thy-1.2 expression cassette can be exploited to study the effects of transgenes during late nervous system development and in the adult, with the added opportunity of analyzing different combinations of expressing and non-expressing neurons in transgenic animals derived from different founder lines.

Animals↗
PubMed1998

Transactivation of Hox gene expression in a VP16-dependent binary transgenic mouse system.

Mice with aberrant expression of Hox genes have provided valuable insight into the role of Hox class transcription factors in patterning the developing skeleton and the nervous system. However, a recurrent problem is the lethality of mice expressing a Hox-transgene. To circumvent premature death frequently associated with transgenes that interfere with development, we have established a binary transgenic mouse system. Transactivator mice harbor the VP16 gene regulated by a promoter of interest while transresponder mice contain the VP16-responsive immediate early (IE) promoter linked to the gene to be expressed [G.W. Byrne, F.H. Ruddle, Multiplex gene regulation: a two-tiered approach to transgene regulation in transgenic mice, Proc. Natl. Acad. Sci. U.S.A., 86 (1989) 5473-5477]. Here, we report the generation of transresponder mouse strains that harbor murine homeobox genes linked to the IE promoter. We provide evidence that these transgenes are transcriptionally activated in progeny that inherit both a transactivator and transresponder transgene. By microdissection of mouse embryos and reverse transcription polymerase chain reaction (RT-PCR) analysis, we demonstrate that the expression of the Hox-transgenes is restricted to those regions of the mouse embryos where VP16 is present. The ability to activate stable Hox-transgenes in a reproducible fashion now permits a detailed in vivo dissection of the molecular mechanisms that lead to developmental abnormalities caused by deregulated Hox-gene expression.

Animals↗
PubMed2001

cis-acting DNA regulatory elements, including the retinoic acid response element, are required for tissue specific laminin B1 promoter/lacZ expression in transgenic mice.

The LAMB1 gene encodes the laminin beta1 subunit of laminin, an extracellular matrix protein. Using several transgenic mouse lines containing various lengths of the LAMB1 promoter driving lacZ reporter gene expression, regions of LAMB1 promoter that contain cis-acting DNA regulatory element(s) have been identified. The 3.9LAMB1betagal transgene is expressed in various tissues during development. LAMB1 transgene expression is observed in a selective set of nephrons of the neonatal and adult kidneys. The cis-acting DNA regulatory elements responsible for LAMB1 transgene expression in ovaries and in juvenile kidneys are present between -'1.4 and -0.7 kb relative to the transcription start site, while those of adult kidneys are located between -2.5 and -1.4 kb. The LAMB1 transgene is also expressed in the epididymis of 1 week old transgenic mice. Mutation of the retinoic acid response element (RARE) in the context of the 3.9LAMB1betagal transgene results in loss of LAMB1 transgene expression in all tissues. Thus, sequences between -2.5 and -0.7 kb plus the RARE are required for appropriate expression of the LAMB1 transgene in mice.

Animals↗
PubMed2001

Co-expression of multiple transgenes in mouse CNS: a comparison of strategies.

The introduction of two transgenes into one animal is increasingly common as transgenic experiments become more sophisticated. In this study we examine two strategies for creating double transgenic founders from a single microinjection. In the first approach, two constructs, each with its own promoter element, were coinjected into the pronucleus. In the second approach, both transgenes were cloned into one vector, separated by an internal ribosomal entry site (IRES), and placed under control of a single promoter. Both strategies save time and increase the percentage of double transgenic offspring over the standard method of mating single transgenic lines. However, despite high transgene copy numbers, the bicistronic lines did not show robust expression of either protein. Copy number and protein expression correlated much better in the coinjected lines, with expression levels in one line approaching that observed in some of our best single transgenic controls. Thus we recommend coinjection of individual plasmids for the generation of multiply transgenic founders.

Amyloid beta-Protein Precursor↗
PubMed1997

Desmin-lacZ transgene expression and regeneration within skeletal muscle transplants.

The purpose of this study was to investigate the initiation and time course of the regeneration process in fragments of skeletal muscle transplants as a function of muscle tissue age at implantation. The appearance of desmin occurs at the very beginning of myogenesis. The transgenic desmin nls lacZ mice used in the study bear a transgene in which the 1 kb DNA 5' regulatory sequence of the desmin gene is linked to a reporter gene coding for Escherichia coli beta-galactosidase. The desmin lacZ transgene labels muscle cells in which the desmin synthesis programme has commenced. We implanted pectoralis muscle fragments from fetal transgenic embryos and mature and old transgenic mice into mature non-transgenic mice. Early events of myogenesis occurring during regeneration started sooner in transplants from 4-month-old (day 3 post-implantation) muscle than in those from 24-month-old (day 5-6 post-implantation) muscle, and they lasted longer in those from young (day 17 post-implantation) than in those from old (day 14 post-implantation) muscle fragments. In adult muscle, transgene activation proceeded from the periphery toward the centre of the transplant. In transplants from fetal 18-day-old pectoralis, myotubes with transgene activity were observed from day 1 to day 19. Desmin immunoreactivity, which appeared about one day after transgene activation, was followed by myosin expression. In adult transplants, the continuity of laminin labelling was disrupted around degenerative fibres, illustrating alteration of the extracellular matrix. Our data suggest that satellite cells from old muscle tissue have lower proliferative capacity and/or less access to trophic substances released by the host (damaged fibres, vascularization) than those from fetal or young adult muscle.

Animals↗
PubMed1999

Effect of p21waf1/cip1 transgene on radiation induced apoptosis in T cells.

The cyclin kinase inhibitor p21WAF1/Cip1 is upregulated by the tumor suppressor p53. While p21 is central for the G-1 arrest mediated by p53, it is still unclear if p21 also functions as a downstream effector of p53 dependent apoptosis. Apoptosis induced by DNA damage but not dexamethasone is p53 dependent in thymocytes. To investigate the physiological role of p21 in apoptosis, we have generated transgenic mice in which the p21 transgene is targeted for restricted expression in the T cell lineage. Thymocytes from p21 transgenic mice were hypersensitive to cell death induced by DNA damaging agents such as ionizing radiation and UV, but not be dexamethasone. Irradiated p21 transgenic thymocytes had approximately twofold more apoptotic cells as compared to irradiated age matched littermate control mice. Radiation induced death is comparable in thymocytes from p21 + Bcl2 + double transgenic mice and age matched littermate controls, indicating that the Bcl2 transgene rescues the radiation hypersensitivity imposed by p21. However, thymocytes from p53-/- mice even when they expressed the p21 transgene, were resistant to death induced by radiation. Together these results show that thymocytes from p21 transgenic mice are hypersensitive to radiation induced programmed cell death and suggest that the radiation hypersensitivity of p21 transgenic thymocytes involves p53 dependent pathway and signals in addition to p21.

Animals↗