Tissue-specific contributions of paternally expressed gene 3 in lactation and maternal care of mus musculus

© 2015 Frey, Kim.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited. Paternally Expressed Gene 3 (Peg3) is an imprinted gene that controls milk letdown and maternal-caring behaviors. In this study, a conditional knockout allele has been developed in Mus musculus to further characterize these known functions of Peg3 in a tissue-specific manner. The mutant line was first crossed with a germline Cre. The progeny of this cross displayed growth retardation phenotypes. This is consistent with those seen in the previous mutant lines of Peg3, confirming the usefulness of the new mutant allele. The mutant line was subsequently crossed individually with MMTV- and Nkx2.1-Cre lines to test Peg3\u27s roles in the mammary gland and hypothalamus, respectively. According to the results, the milk letdown process was impaired in the nursing females with the Peg3 mutation in the mammary gland, but not in the hypothalamus. This suggests that Peg3\u27s roles in the milk letdown process are more critical in the mammary gland than in the hypothalamus. In contrast, one of the maternal-caring behaviors, nest-building, was interrupted in the females with the mutation in both MMTV- and Nkx2.1-driven lines. Overall, this is the first study to introduce a conditional knockout allele of Peg3 and to further dissect its contribution to mammalian reproduction in a tissue-specific manner

APeg3: Regulation of Peg3 through an evolutionarily conserved ncRNA

Mammalian APeg3 is an antisense gene that is localized within the 3\u27-untranslated region of the imprinted gene, Peg3. APeg3 is expressed only in the vasopressinergic neurons of the hypothalamus, thus is predicted to play significant roles in this specific area of the brain. In the current study, we investigate the functions of APeg3 with comparative genomics and cell line-based functional approaches. The transcribed region of APeg3 displays high levels of sequence conservation among placental mammals, but without any obvious open reading frame, suggesting that APeg3 may have been selected as a ncRNA gene during eutherian evolution. This has been further supported by the detection of a conserved local RNA secondary structure within APeg3. RNA secondary structure analyses indicate a single conserved hairpin-loop structure towards the 5\u27 end of the transcript. The results from cell line-based transfection experiments demonstrate that APeg3 has the potential to down-regulate the transcription and protein levels of Peg3. The observed down-regulation by APeg3 is also somewhat orientation-independent. Overall, these results suggest that APeg3 has evolved as a ncRNA gene and controls the function of its sense gene Peg3 within specific neuronal cells. © 2014 Elsevier B.V

Towards a strong coupling theory for the KPZ equation

After a brief introduction we review the nonperturbative weak noise approach to the KPZ equation in one dimension. We argue that the strong coupling aspects of the KPZ equation are related to the existence of localized propagating domain walls or solitons representing the growth modes; the statistical weight of the excitations is governed by a dynamical action representing the generalization of the Boltzmann factor to kinetics. This picture is not limited to one dimension. We thus attempt a generalization to higher dimensions where the strong coupling aspects presumably are associated with a cellular network of domain walls. Based on this picture we present arguments for the Wolf-Kertez expression z= (2d+1)/(d+1) for the dynamical exponent.Comment: 10 pages, 4 figures, "Horizons in Complex Systems", Messina, December 2001 (H. E. Stanley, 60th birthday

On the Renormalization of the Kardar-Parisi-Zhang equation

The Kardar-Parisi-Zhang (KPZ) equation of nonlinear stochastic growth in d dimensions is studied using the mapping onto a system of directed polymers in a quenched random medium. The polymer problem is renormalized exactly in a minimally subtracted perturbation expansion about d = 2. For the KPZ roughening transition in dimensions d > 2, this renormalization group yields the dynamic exponent z* = 2 and the roughness exponent chi* = 0, which are exact to all orders in epsilon = (2 - d)/2. The expansion becomes singular in d = 4, which is hence identified with the upper critical dimension of the KPZ equation. The implications of this perturbation theory for the strong-coupling phase are discussed. In particular, it is shown that the correlation functions and the coupling constant defined in minimal subtraction develop an essential singularity at the strong-coupling fixed point.Comment: 21 pp. (latex, now texable everywhere, no other changes), with 2 fig

Allele and dosage specificity of the Peg3 imprinted domain

© 2018 Bretz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The biological impetus for gene dosage and allele specificity of mammalian imprinted genes is not fully understood. To address this, we generated and analyzed four sets of mice from a single breeding scheme with varying allelic expression and gene dosage of the Peg3 domain. The mutants with abrogation of the two paternally expressed genes, Peg3 and Usp29, showed a significant decrease in growth rates for both males and females, while the mutants with biallelic expression of Peg3 and Usp29 resulted in an increased growth rate of female mice only. The mutant cohort with biallelic expression of Peg3 and Usp29 tended to have greater numbers of pups compared to the other genotypes. The mutants with switched active alleles displayed overall similar phenotypes to the wild type, but did show some differences in gene expression, suggesting potential non-redundant roles contributed by the maternal and paternal alleles. Overall, this study demonstrates a novel in vivo approach to investigate the allele and dosage specificity of mammalian imprinted domains

Asymptotic behavior of the loss probability for an M/G/1/N queue with vacations

In this paper, asymptotic properties of the loss probability are considered for an M/G/1/N queue with server vacations and exhaustive service discipline, denoted by an M/G/1/N -(V, E)-queue. Exact asymptotic rates of the loss probability are obtained for the cases in which the traffic intensity is smaller than, equal to and greater than one, respectively. When the vacation time is zero, the model considered degenerates to the standard M/G/1/N queue. For this standard queueing model, our analysis provides new or extended asymptotic results for the loss probability. In terms of the duality relationship between the M/G/1/N and GI/M/1/N queues, we also provide asymptotic properties for the standard GI/M/1/N model

Imprinting control region (ICR) of the Peg3 domain

The imprinting and transcription of the 500 kb genomic region surrounding the mouse Peg3 is predicted to be regulated by the Peg3-differentially methylated region (DMR). In the current study, this prediction was tested using a mutant mouse line lacking this potential imprinting control region (ICR). At the organismal level, paternal and maternal transmission of this knockout (KO) allele caused either reduced or increased growth rates in the mouse, respectively. In terms of the imprinting control, the paternal transmission of the KO allele resulted in bi-allelic expression of the normally maternally expressed Zim2, whereas the maternal transmission switched the transcriptionally dominant allele for Zfp264 (paternal to maternal). However, the allele-specific DNA methylation patterns of the DMRs of Peg3, Zim2 and Zim3 were not affected in the mice that inherited the KO allele either paternally or maternally. In terms of the transcriptional control, the paternal transmission caused a dramatic down-regulation in Peg3 expression, but overall up-regulation in the other nearby imprinted genes. Taken together, deletion of the Peg3-DMR caused global changes in the imprinting and transcription of the Peg3 domain, confirming that the Peg3-DMR is an ICR for this imprinted domain. © The Author 2012. Published by Oxford University Press. All rights reserved

Allele-specific enhancer interaction at the Peg3 imprinted domain

Copyright: © 2019 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The parental allele specificity of mammalian imprinted genes has been evolutionarily well conserved, although its functional constraints and associated mechanisms are not fully understood. In the current study, we generated a mouse mutant with switched active alleles driving the switch from paternal-to-maternal expression for Peg3 and the maternal-to-paternal expression for Zim1. The expression levels of Peg3 and Zim1, but not the spatial expression patterns, within the brain showed clear differences between wild type and mutant animals. We identified putative enhancers localized upstream of Peg3 that displayed allele-biased DNA methylation, and that also participate in allele-biased chromosomal conformations with regional promoters. Most importantly, these data suggest for the first time that long-distance enhancers may contribute to allelic expression within imprinted domains through allele-biased interactions with regional promoters