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A Paldi

Publications and source records attributed to A Paldi.

11 recordsLinked to original sources
PubMed2004

Differential expression and imprinting status of Ins1 and Ins2 genes in extraembryonic tissues of laboratory mice.

There are two functional insulin genes in the mouse genome. The Ins2 gene is imprinted and expressed monoallelically from the paternal allele in the yolk sac. In the present study we have re-examined the imprinting status of Ins1. We found that Ins1 is not expressed in the yolk sac of several laboratory mouse strains. The asynchrony of replication at the wild type locus was significantly lower than at imprinted loci and was more similar to non-imprinted loci. Finally, we have taken the advantage of the Ins1(neo) allele created by homologous recombination to examine the allelic usage at this locus. We observed that the neo gene inserted at the Ins1 locus was expressed from both the paternally and the maternally transmitted allele. Therefore, the Ins1 gene does not share any of the basic properties of imprinted genes. On the basis of these data, we concluded that Ins1 locus is unlikely to be imprinted in common laboratory mice.

Alleles↗
PubMed2001

Did genomic imprinting and X chromosome inactivation arise from stochastic expression?

Both X chromosome inactivation and autosomal genomic imprinting generate a functional hemizygosity. Here we consider models that explain the evolution of genomic imprinting and X chromosome inactivation from novel perspectives. Specifically, we suggest that random (in)activation events are common in genes and gene clusters with a low probability of transcription. These generate variability that natural selection has acted on to evolve stable monoallelic expression. Possible selection forces might include a need for dosage compensation and the prevention of biallelic silencing where a total switch off would be lethal. Two different mechanisms can accomplish regular monoallelic expression - genomic imprinting and gene counting.

Animals↗
PubMed1999

Biallelic transcription of Igf2 and H19 in individual cells suggests a post-transcriptional contribution to genomic imprinting.

The H19 and insulin-like growth factor 2 (Igf2) genes in the mouse are models for genomic imprinting during development. The genes are located only 90 kb apart in the same transcriptional orientation [1], but are reciprocally imprinted: Igf2 is paternally expressed while H19 is maternally expressed. It has been suggested that expression of H19 and repression of Igf2 (or the converse) on a given chromosome are mechanistically linked and that the parental imprint operates at the level of transcription [2]. Although expression of Igf2 and H19 is thought to be monoallelic, the data have so far been obtained exclusively by looking at steady-state RNA levels using techniques that reflect the average activity of the genes in a cell population [3] [4]. Here, we have adapted a fluorescent in situ hybridisation (FISH) method to detect nascent RNA molecules of Igf2 and H19 at the initial transcription sites in the nuclei of wild-type mouse embryonic liver cells. Nine different transcription patterns were observed, reflecting a high heterogeneity of transcription at the single-cell level. Our observations suggest that regulation of Igf2 and H19 by parental imprinting is much more complex than previously proposed and acts at both transcriptional and post-transcriptional levels.

Alleles↗
PubMed1999

The genotype and epigenotype synergize to diversify the spatial pattern of expression of the imprinted H19 gene.

Little is known of how the genetic background effects the phenomenon of genomic imprinting. The H19 gene belongs to a cluster of imprinted genes on human chromosome 11. Here we show that the alternative splicing of a human H19 transcript is genotype-specific. Moreover, this variant transcript, which lacks exon 4, is either not found at all, is widely expressed or is confined to extra-villous cytotrophoblasts in first trimester placenta, depending on a combination of the genotype and the sex of the transmitting parent.

Alleles↗
PubMed1998

Early recognition of pregnancy by the maternal immune system.

PROBLEM: Immunologic recognition of pregnancy is important for normal gestation. Successful pregnancy is characterized by a Th2 dominance, whereas there is a Th1 dominance in failed pregnancies. We assume that a signal given by the fertilized ovum induces a Th2 shift, necessary for a normal outcome. In vitro fertilization provides a tool for testing this possibility. METHOD OF STUDY: Phytohemagglutinin-stimulated lymphocytes were incubated for 48 hr in the presence of culture media from in vitro fertilized eggs, as well as in follicular fluid (FF) and control supernatants. Total RNA was isolated from the lymphocytes by the guanidine-isothiocyanate method and interleukin (IL)-10 mRNA expression was detected by reverse transcription-polymerase chain reaction. RESULTS: Ten percent of the activated lymphocytes incubated with FF expressed IL-10 mRNA, whereas 88% of the lymphocytes activated with supernatants of sperm + oocytes gave a positive signal. Significantly (P < 0.05) fewer (50%) lymphocytes stimulated in the presence of control supernatants also expressed mRNA for IL-10. In supernatants of activated lymphocytes incubated with the culture medium of spermia + oocytes, the concentration of IL-10 was significantly higher than in the lymphocytes incubated with FF. CONCLUSION: These data suggest that the presence of the fertilized ovum induces a Th2 shift, which enables pregnancy to proceed to term.

Base Sequence↗
PubMed1993

Cis effect of lacZ sequences in transgenic mice.

Transgenic mice carrying the 3-hydroxy-3-methylglutarylCoA reductase (HMG) promoter driving the Escherichia coli beta-galactosidase (lacZ) gene did not display the expected ubiquitous and constitutive expression in HMG-lacZ transgenic mice. The same promoter is however able to drive ubiquitous expression of the chloramphenicol acetyltransferase (cat) gene. Two lines of double HMG-lacZ and HMG-cat transgenic mice were obtained in which the two constructs were integrated at the same genomic sites. These mice expressed both reporter genes, but exclusively in the testes. These results suggest that the lacZ sequence might interfere negatively with the expression of the adjacent HMG-cat transgene.

Animals↗
PubMed1991

Genetically identical parthenogenetic mouse embryos produced by inhibition of the first meiotic cleavage with cytochalasin D.

The microfilament inhibitor cytochalasin D inhibits extrusion of the first polar body when present during the first meiotic division of mouse oocytes; however, it does not interfere with anaphase movement of chromosomes, and thus induces the formation of tetraploid oocytes. After the separation of chromosomes in anaphase, two spindles start to assemble. However, they merge rapidly and a single meiotic spindle forms. During the transition between metaphase I and metaphase II, in the presence of cytochalasin D, a drop in histone kinase activity takes place demonstrating a transitional decrease in the activity of the maturation promoting factor. These oocytes can be activated parthenogenetically a few hours after washing out the inhibitor. After completion of the second meiotic division and extrusion of a polar body, they contain a diploid number of chromosomes. They are genetically identical to each other and to their mother. Such eggs develop to the blastocyst stage and can implant in the uteri of foster mothers. Most of these fetuses die before the 9th day of gestation, as do diploid control fetuses treated with cytochalasin D during the second meiotic division. The heterozygous state of the experimental embryos obtained after activation of eggs recovered from heterozygous females and treated with cytochalasin D during the first meiotic division was confirmed using a glucose-phosphate isomerase assay. This technique allows the production of genetic clones of parthenogenetic embryos by simple means.

Animals↗
PubMed1991

Polyclonal origin of pancreatic islets in aggregation mouse chimaeras.

In the present study, we have examined the origin and growth pattern of the beta cells in pancreatic islets, to determine whether a single progenitor cell gave rise to all the precursors of the islets, or if each of a few progenitor cells is the founder of a different islet, or if each islet is a mixture of cells originating from a pool of progenitor cells. Aggregation mouse chimaeras where the pancreatic beta cells derived from each embryo can be identified in the islets on histological sections were analyzed. In two chimaeras, all the islets contained cells from both the aggregated embryo. This clearly demonstrates that each islet resulted from several independent cells. In addition, the beta cells derived from either embryo component were in very small clusters in the islets, suggesting that in situ cell division did not account significantly for islet growth.

Animals↗
PubMed1989

Postnatal development of parthenogenetic in equilibrium with fertilized mouse aggregation chimeras.

Chimeras were made from parthenogenetic and fertilized cleavage-stage mouse embryos. The perinatal mortality was high. The parthenogenetic contributions to different tissues at birth ranged from 0 to 50%. No selection of parthenogenetic cells was observed in the pigmentation of the coat, but this does not exclude that such selection could act in other tissues. The weight of chimeras at birth negatively correlated to the average contribution of the parthenogenetic part. The growth rate of chimeras was lower than that of nonchimeric animals. The data presented demonstrated that, although parthenogenetic cells are not cell lethals and they can participate to some degree in normal development of most tissues, their extensive presence reduces the viability of chimeras and retards the postnatal development.

Animals↗