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1.
Anim Genet ; 45(4): 589-92, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24797173

RESUMO

Growth traits, such as body weight and carcass body length, directly affect productivity and economic efficiency in the livestock industry. We performed a genome-wide linkage analysis to detect the quantitative trait loci (QTL) that affect body weight, growth curve parameters and carcass body length in an F2 intercross between Landrace and Korean native pigs. Eight phenotypes related to growth were measured in approximately 1000 F2 progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The least squares regression approach was used to conduct the QTL analysis. For body weight traits, we mapped 16 genome-wide significant QTL on SSC1, 3, 5, 6, 8, 9 and 12 as well as 22 suggestive QTL on SSC2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 17. On SSC12, we identified a major QTL affecting body weight at 140 days of age that accounted for 4.3% of the phenotypic variance, which was the highest test statistic (F-ratio = 45.6 under the additive model, nominal P = 2.4 × 10(-11) ) observed in this study. We also showed that there were significant QTL on SSC2, 5, 7, 8, 9 and 12 affecting carcass body length and growth curve parameters. Interestingly, the QTL on SSC2, 3, 5, 6, 8, 9, 10, 12 and 17 influencing the growth-related traits showed an obvious trend for co-localization. In conclusion, the identified QTL may play an important role in investigating the genetic structure underlying the phenotypic variation of growth in pigs.


Assuntos
Ligação Genética , Locos de Características Quantitativas , Sus scrofa/fisiologia , Animais , Tamanho Corporal , Peso Corporal , Cruzamentos Genéticos , Repetições de Microssatélites , Reação em Cadeia da Polimerase/veterinária , Sus scrofa/genética , Sus scrofa/crescimento & desenvolvimento
2.
Nat Genet ; 29(2): 201-5, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11586302

RESUMO

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.


Assuntos
Mapeamento Cromossômico , Genoma , Células Híbridas/efeitos da radiação , Animais , Etiquetas de Sequências Expressas , Camundongos
3.
Klin Khir ; (7): 5-8, 2012 Jul.
Artigo em Ucraniano | MEDLINE | ID: mdl-23033768

RESUMO

Results of surgical treatment of 93 primary patients with medullary thyroid carcinoma within 1995-2009 years, including 26 (28%) - with hereditary disease (MEN2 syndrome) were analyzed. The best long-term results were observed in group of noninvasive tumor without metastases at the time of operation (39% - clinical and biochemical recovery, 32% - clinical remission). No one patient with extrathyroid tumor invasion and regional/distant metastases has completely recovered. Hereditary forms of disease are more aggressiveness in comparison with sporadic carcinomas with higher rate of distant metastases (31 and 21%) and worse survival. In sporadic group 3 (6%) patients and in hereditary group - 4 (12%) died from progression of distant metastases within 8-15 years after primary operation. Complete recovery was seen only after radical primary operations. Repeated surgery was palliative. Implementation of calcitonine screening and genetic testing for Ret-protooncogene mutation is an important task for Ukraine medicine to improve results of medullary carcinoma treatment.


Assuntos
Carcinoma Medular/secundário , Carcinoma Medular/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Idade de Início , Idoso , Carcinoma Medular/genética , Carcinoma Medular/mortalidade , Comorbidade , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/mortalidade , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/genética , Resultado do Tratamento
4.
Anim Genet ; 42(6): 621-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22035003

RESUMO

Haematological traits play important roles in disease resistance and defence functions. The objective of this study was to locate quantitative trait loci (QTL) and the associated positional candidate genes influencing haematological traits in an F(2) intercross between Landrace and Korean native pigs. Eight blood-related traits (six erythrocyte traits, one leucocyte trait and one platelet trait) were measured in 816 F(2) progeny. All experimental animals were genotyped with 173 informative microsatellite markers located throughout the pig genome. We report that nine chromosomes harboured QTL for the baseline blood parameters: genomic regions on SSC 1, 4, 5, 6, 8, 9, 11, 13 and 17. Eight of twenty identified QTL reached genome-wide significance. In addition, we evaluated the KIT locus, an obvious candidate gene locus affecting variation in blood-related traits. Using dense single nucleotide polymorphism marker data on SSC 8 and the marker-assisted association test, the strong association of the KIT locus with blood phenotypes was confirmed. In conclusion, our study identified both previously reported and novel QTL affecting baseline haematological parameters in pigs. Additionally, the positional candidate genes identified here could play an important role in elucidating the genetic architecture of haematological phenotype variation in swine and in humans.


Assuntos
Plaquetas/citologia , Eritrócitos/citologia , Leucócitos/citologia , Locos de Características Quantitativas , Sus scrofa/genética , Animais , Cruzamentos Genéticos , Estudo de Associação Genômica Ampla , Hematopoese , Especificidade da Espécie , Sus scrofa/metabolismo
5.
Anim Genet ; 42(4): 451-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21749430

RESUMO

The KIT locus has been suggested to be a strong candidate region linked with whole-body roan in the F(2) population produced by intercrosses between Landrace and Korean Native pigs. In this manuscript, we report the finding of a novel alternative splicing event in the porcine KIT gene that results in the skipping of exon 5 in the I(Rn) allele. KIT mRNAs that lack exon 5 were identified in the large intestine and skin, suggesting that the mechanism responsible for the skipping of exon 5 may be tissue specific. A U(26) repeat in intron 5 showed complete linkage (LOD = 11.8) with the roan phenotype and absolute association with the black phenotype of the Korean Native pig (KNP) population samples, inferring that the repeat pattern may alter the complementary base-pairing-mediated looping-out of introns 4 and 5, which may mediate the exon 5-skipping event. Although the sample size in our study was relatively small, we speculate that the R3 allele containing the U(26) repeat is a causative element for the roan phenotype via alternative control of the exon skipping in our roan pedigree.


Assuntos
Processamento Alternativo/genética , Éxons/genética , Cabelo/fisiologia , Pigmentação/genética , Proteínas Proto-Oncogênicas c-kit/genética , RNA Mensageiro/genética , Sus scrofa/genética , Animais , Sequência de Bases , Cruzamentos Genéticos , Primers do DNA/genética , Ligação Genética , Genética Populacional , Dados de Sequência Molecular , Linhagem , Pigmentação/fisiologia , República da Coreia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Sus scrofa/fisiologia
7.
AJNR Am J Neuroradiol ; 28(10): 1895-901, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17921235

RESUMO

BACKGROUND AND PURPOSE: The outcome for simultaneous revascularization of more than 1 supra-aortic arterial stenosis has not been evaluated because of concerns regarding the increased risk of additional procedures. We evaluated the feasibility and safety of concomitant multiple supra-aortic arterial revascularizations (CMSAR). MATERIALS AND METHODS: We retrospectively evaluated 50 consecutive patients who underwent CMSARs with angioplasty and stent placement. The study included a separate lesion group (LG) (n = 28), ipsilateral LG (n = 17) including adjacent (n = 6) and remote (n = 11) tandem lesions, and triple LG (n = 5). We assessed the procedural success (defined as residual stenosis <30%) and periprocedural event rate (ER) (minor or major stroke, and death). We compared the ERs in the lesion (ipsilateral vs separate) and symptom (unstable vs stable) pattern groups with the Fisher exact test. RESULTS: Procedural success was achieved in all patients (50/50). Periprocedural events within 30 days were noted in 5 (10%). ER within 2 days after the procedure was higher in the ipsilateral LG (4/17) than in the separate LG (0/28) (P = .016). Major events consisting of a major stroke and a death occurred in 2 patients in the unstable group (4%) and was more common in the unstable (2 of 7) than in the stable group (0/38) (P = .029). During the mean 11-month follow-up period, there was 1 symptomatic recurrence. CONCLUSION: CMSARs are feasible with a high procedural success rate resulting in a favorable short-term outcome. However, they must be carefully performed in ipsilateral LG, especially in patients in the unstable group.


Assuntos
Angioplastia com Balão , Doenças das Artérias Carótidas/terapia , Arteriosclerose Intracraniana/terapia , Stents , Síndrome do Roubo Subclávio/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Doenças das Artérias Carótidas/diagnóstico por imagem , Angiografia Cerebral , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Stents/efeitos adversos , Acidente Vascular Cerebral/etiologia , Síndrome do Roubo Subclávio/diagnóstico por imagem , Insuficiência Vertebrobasilar/terapia
8.
Curr Top Dev Biol ; 120: 103-24, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27475850

RESUMO

Zygotic genome activation (ZGA, a.k.a. zygotic gene activation) is a critical event in development, when the paternally derived genome and maternally derived genome begin to be activated and transcribed after fertilization. Major ZGA occurs at the two-cell stage in mice and the four- to eight-cell stage in human preimplantation embryos. It has been thought that ZGA exists to provide RNAs and proteins supporting embryonic development after supplies stored in oocytes are used up; however, this paradigm does not seem to explain recent findings. For example, many ZGA genes-once activated-are quickly turned off, and thus ZGA forms a transient wave of transcriptional activation. In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation embryos during ZGA. Detailed molecular analyses of Zscan4 expression and function have revealed common features of Zscan4-associated events (Z4 events) in mouse embryonic stem cells and ZGA in preimplantation embryos. One feature is a rapid derepression and rerepression of constitutive heterochromatin, which includes pericentromeric major satellites and telomeres, and facultative heterochromatin, which includes retrotransposons and Z4 event-associated genes. We propose that the Z4 event superimposed on ZGA plays a critical role in the maintenance of genome and chromosome integrity in preimplantation embryos by promoting correction of DNA damage and chromosome abnormalities.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Genoma , Fatores de Transcrição/metabolismo , Zigoto/metabolismo , Animais , Dano ao DNA , Evolução Molecular , Humanos
9.
Int J Dev Biol ; 42(7): 1051-65, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9853837

RESUMO

It is difficult to study gene expression in mammalian embryonic germ cells as PGCs constitute only a minor proportion of the mouse embryo. We have overcome this problem by using a novel combination of established molecular and transgenic approaches. A line of mice has been generated in which the cells of the germ lineage express the beta-galactosidase reporter gene during embryogenesis. Using this line, germ cells have been purified to near homogeneity from embryos at discrete stages during germline development by use of a stain for beta-gal activity and a fluorescence activated cell sorter. Subsequently, cDNA libraries have been constructed from each germ cell population using a modified lone-linker PCR strategy. These combined cDNA libraries represent genes expressed in PGCs during mammalian germline development. To facilitate a molecular genetic approach to studying mammalian germline development, these cDNA libraries will be pooled to form an arrayed, addressed reference embryonic germ cell cDNA library. In parallel with large-scale cDNA sequencing efforts; genes that are differentially expressed in germ cells will be identified by screening the reference library with probes generated by subtractive hybridization. Complementary DNAs identified using this approach will be analyzed by sequencing, database comparison, genomic mapping and in situ hybridization to ascertain the potential functional importance of each gene to germline development. In addition to providing a wealth of novel information regarding patterns of gene expression during mammalian germline development, these results will form the basis for future experiments to determine the function of these genes in this process.


Assuntos
Expressão Gênica , Células Germinativas/fisiologia , Mamíferos/embriologia , Animais , Linhagem Celular , Feminino , Biblioteca Gênica , Masculino , Camundongos , Camundongos Transgênicos , Diferenciação Sexual
10.
AJNR Am J Neuroradiol ; 36(6): 1188-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25678480

RESUMO

BACKGROUND AND PURPOSE: Diagnostic test accuracy studies for ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy have shown inconclusive results due to their heterogenous study designs. Our aim was to compare the diagnostic accuracy of ultrasonography-guided fine-needle aspiration versus ultrasonography-guided core needle biopsy for detecting malignant tumors of the salivary gland and for the tissue-specific diagnosis of salivary gland tumors in a single tertiary hospital. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and informed consent was waived. Four hundred twelve patients who underwent ultrasonography-guided fine-needle aspiration (n = 155) or ultrasonography-guided core needle biopsy (n = 257) with subsequent surgical confirmation or clinical follow-up were enrolled. We compared the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy regarding malignant salivary gland tumors and the correct tissue-specific diagnosis of benign and malignant tumors. We also tested the difference between these procedures according to the operator's experience and lesion characteristics. RESULTS: The inconclusive rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 19% and 4%, respectively (P < .001). The overall accuracy of ultrasonography-guided core needle biopsy for diagnosing malignant tumors was significantly higher than that of ultrasonography-guided fine-needle aspiration (P = .024). The correct tissue-specific diagnosis rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 95% versus 97% for benign tumors (P = .648) and 67% versus 80% for malignant tumors (P = .310). Trainees showed significantly lower accuracy with ultrasonography-guided fine-needle aspiration than with ultrasonography-guided core needle biopsy for diagnosing malignant tumors (P = .021). There was no difference between the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy according to the internal composition of the lesions. There were no complications requiring intervention or hospitalization in our patients. CONCLUSIONS: Ultrasonography-guided core needle biopsy is superior to ultrasonography-guided fine-needle aspiration in detecting and characterizing malignant tumors of the salivary gland and could emerge as the diagnostic method of choice for patients presenting with a salivary gland mass.


Assuntos
Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre/métodos , Glândulas Salivares/patologia , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Criança , Feminino , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Sensibilidade e Especificidade , Adulto Jovem
11.
Trends Biotechnol ; 19(12): 511-8, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11711195

RESUMO

Fundamental questions in developmental biology are: what genes are expressed, where and when they are expressed, what is the level of expression and how are these programs changed by the functional and structural alteration of genes? These questions have been addressed by studying one gene at a time, but a new research field that handles many genes in parallel is emerging. The methodology is at the interface of large-scale genomics approaches and developmental biology. Genomics needs developmental biology because one of the goals of genomics--collection and analysis of all genes in an organism--cannot be completed without working on embryonic tissues in which many genes are uniquely expressed. However, developmental biology needs genomics--the high-throughput approaches of genomics generate information about genes and pathways that can give an integrated view of complex processes. This article discusses these new approaches and their applications to mammalian developmental biology.


Assuntos
Biologia do Desenvolvimento/tendências , Perfilação da Expressão Gênica/métodos , Genômica/tendências , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Estruturas Embrionárias/citologia , Estruturas Embrionárias/embriologia , Etiquetas de Sequências Expressas , Biblioteca Gênica , Humanos , Hibridização In Situ , Camundongos , Proteoma
12.
J Invest Dermatol ; 107(1): 41-3, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8752837

RESUMO

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small tumors predominantly on the face. To map the causative gene, we performed linkage analysis with microsatellite markers in three American families. We found a significant linkage of a gene for MFT to chromosome 9p2l. The maximum combined lod score was 3.31 at D9S171 at theta = 0. The disease locus was defined to a 4-cM region between IFNA and D9S126. Because several tumor suppressor genes including p16 and p15 have been mapped to this region, the gene for MFT may also be a tumor suppressor.


Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 9 , Genes , Neoplasia de Células Basais/genética , Neoplasias Cutâneas/genética , Ligação Genética , Humanos , Linhagem
13.
Gene ; 84(2): 383-9, 1989 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-2558971

RESUMO

A new gene expression system in mammalian cells was developed by using the glucocorticoid receptor (GR) as an inducible positive feedback factor. Mouse Ltk- cells were transfected with plasmids carrying the GR-encoding gene and the lacZ reporter gene, both of which were fused with the glucocorticoid-inducible enhancer/promotor of the mouse mammary tumor virus (MTV). The GR gene was first induced to supply the receptor protein, which further induced the expression of both GR and reporter genes. Stable transformants induced with dexamethasone, a synthetic glucocorticoid hormone, demonstrated beta-galactosidase activity 60-140-fold higher than uninduced controls. Similarly, the human alpha-interferon-encoding gene fused with the MTV enhancer/promoter was induced more than 12,000-fold. This system allowed us to increase the expression of the reporter or target genes without augmenting basal levels of expression significantly, and may be useful to investigate the unknown function of a cloned gene, particularly when the gene product of interest is cytotoxic or growth-inhibiting.


Assuntos
Regulação da Expressão Gênica , Vetores Genéticos , Receptores de Glucocorticoides/genética , Transformação Genética , Animais , Células Cultivadas , Clonagem Molecular , Dexametasona , Retroalimentação , Humanos , Immunoblotting , Interferon Tipo I/genética , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Plasmídeos , Regiões Promotoras Genéticas , Ratos , beta-Galactosidase/genética
14.
J Nanosci Nanotechnol ; 1(2): 185-90, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12914050

RESUMO

Three ternary and four quaternary hafnium-based alloys have been rapidly solidified, and the devitrification of the resultant metallic glasses has been studied to evaluate the influence of composition on the products. The formation of metastable and stable Fd3m (Pearson symbol cF96) Ti2Ni was evident whenever the alloy composition in the stable equilibrium diagrams showed this phase. The replacement of nickel by iron led to the appearance of this phase in preference to the icosahedral quasicrystal. Several common features of the amorphous alloys that form either nanoscale icosahedral or cF96 Ti2Ni-type phases on devitrification are discussed and summarized.


Assuntos
Ligas/química , Cristalização/métodos , Háfnio/química , Nanotecnologia/métodos , Níquel/química , Titânio/química , Varredura Diferencial de Calorimetria , Vidro/química , Metais/química , Microscopia Eletrônica , Conformação Molecular , Tamanho da Partícula , Temperatura , Difração de Raios X
15.
AJNR Am J Neuroradiol ; 33(1): 124-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22158923

RESUMO

BACKGROUND AND PURPOSE: The US features of benign and malignant nodules overlap, and benign thyroid lesions can mimic thyroid malignancy on US. Benign cystic nodules after spontaneous collapse or needle aspiration, can mimic malignant thyroid nodules. Our aim was to evaluate the US features of CBCNs of the thyroid that distinguish such nodules from malignant thyroid nodules. MATERIALS AND METHODS: US and clinical findings in 13 patients, each with a single CBCN, were evaluated to determine if they showed >50% cystic content on initial US or CT and >30% decrease in maximum diameter on follow-up US. We compared these findings with those of 26 patients, each with a single surgically confirmed PTMC. US scans were analyzed for internal content, shape, margin, echogenicity, presence of echogenic dots suggesting micro- and macrocalcification, inner isoechoic rim, and low-echoic halo. RESULTS: Six of the 13 (46%) CBCNs were classified as malignant on US due to their marked hypoechogenicity, microcalcification, or spiculated margins. US features that differed between CBCNs and PTMCs were shape (ovoid-to-round versus taller-than-wide, P = .016); margins (ill-defined versus spiculated, P < .000); low-echoic halo (P < .000); inner isoechoic rim (P < .000) with high negative predictive values (100%, 91%, 91%, and 89%, respectively); and clinically acceptable diagnostic accuracy (59%, 80%, 82%, and 85%, respectively). CONCLUSIONS: US features helpful for differential diagnosis of CBCNs from PTMCs include shape, margin, and the presence of an inner isoechoic rim and a low-echoic halo. Familiarity with US features suggesting CBCNs may be helpful in reducing unnecessary repeated FNABs.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Cistos/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Reproduction ; 132(1): 45-57, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16816332

RESUMO

A series of Ca(2+) oscillations during mammalian fertilization is necessary and sufficient to stimulate meiotic resumption and pronuclear formation. It is not known how effectively development continues in the absence of the initial Ca(2+) signal. We have triggered parthenogenetic egg activation with cycloheximide that causes no Ca(2+) increase, with ethanol that causes a single large Ca(2+) increase, or with Sr(2+) that causes Ca(2+) oscillations. Eggs were co-treated with cytochalasin D to make them diploid and they formed pronuclei and two-cell embryos at high rates with each activation treatment. However, far fewer of the embryos that were activated by cycloheximide reached the blastocyst stagecompared tothose activated by Sr(2+) orethanol. Any cycloheximide-activated embryos that reached the blastocyst stage had a smaller inner cell mass number and a greater rate of apoptosis than Sr(2+)-activated embryos. The poor development of cycloheximide-activated embryos was due to the lack of Ca(2+) increase because they developed to blastocyst stages at high rates when co-treated with Sr(2+) or ethanol. Embryos activated by either Sr(2+) or cycloheximide showed similar signs of initial embryonic genome activation (EGA) when measured using a reporter gene. However, microarray analysis of gene expression at the eight-cell stage showed that activation by Sr(2+) leads to a distinct pattern of gene expression from that seen with embryos activated by cycloheximide. These data suggest that activation of mouse eggs in the absence of a Ca(2+) signal does not affect initial parthenogenetic events, but can influence later gene expression and development.


Assuntos
Blastocisto/metabolismo , Sinalização do Cálcio , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Partenogênese , Animais , Apoptose , Proliferação de Células , Fase de Clivagem do Zigoto , Cicloeximida/farmacologia , Técnicas de Cultura Embrionária , Etanol/farmacologia , Feminino , Perfilação da Expressão Gênica/métodos , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos , Análise de Sequência com Séries de Oligonucleotídeos , Inibidores da Síntese de Proteínas/farmacologia
19.
Bioessays ; 14(5): 341-6, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1637366

RESUMO

A new field of gene expression regulation research is emerging that has previously been overlooked. This new area is concerned with distinguishing the expression of a single gene from the averaged expression of many gene copies within the cell population. This paper reviews research focused on individual genes in inducible gene expression systems. The main experimental strategy is to measure the gene expression level of a single cell containing a single reporter gene molecule. In contrast to the commonly held belief, gene induction is found to be stochastic under certain conditions. The possible mechanisms and implications are discussed.


Assuntos
Regulação da Expressão Gênica , Cinética , Ativação Transcricional
20.
J Theor Biol ; 153(2): 181-94, 1991 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-1787735

RESUMO

Expression levels of individual copies of an inducible gene have been presumed to be identical to the averaged level of many copies and to change in a smooth and predictable way according to the concentration of an inducing molecule. However, our recent experiments using a steroid-inducible system showed that the expression levels of individual copies are very heterogeneous and do not necessarily coincide with the averaged expression level of many copies (Ko et al., 1990, EMBO J. 9, 2835-2842). To explain this result, I present a stochastic model for gene induction here and its analysis using computer simulation. Stochasticity in the model is derived from the randomness corresponding to the random timing of molecular collisions and dissociations between transcription factors and a gene copy, since at any instant each copy is thought to be either "switched on" by having a transcription complex bound to it, or "switched off" by not having a transcription complex bound. This model can produce two types of gene induction that depend on the stability of the transcription complex on the regulatory region of the gene. An unstable transcription complex causes a homogeneous level of gene induction among individual copies, while a stable transcription complex causes a heterogeneous level. Since the recent consensus formed by in vitro transcription experiments is that the transcription complex is generally very stable, the latter case (the non-deterministic one) is highly possible. Since typical eukaryotic cells have just two copies for any gene in a single cell, this possibility of heterogeneous gene induction indicates that the phenotypes of individual cells cannot be precisely determined by just environmental signals, such as inducers. This may prompt us to reconsider many problems related to gene induction, including morphogenesis.


Assuntos
Simulação por Computador , Regulação da Expressão Gênica/fisiologia , Modelos Genéticos , Animais , Camundongos , Morfogênese/genética , Fatores de Transcrição/fisiologia , Ativação Transcricional , beta-Galactosidase/genética
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