scholarly journals Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development

2007 ◽  
Vol 17 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Rocío M. Rivera ◽  
Paula Stein ◽  
Jamie R. Weaver ◽  
Jesse Mager ◽  
Richard M. Schultz ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Imprinted Genes ◽  
Aberrant Expression

Mouse embryos with paternal duplication of an imprinted chromosome 7 region die at midgestation and lack placental spongiotrophoblast

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 265-270 ◽  
Author(s):  
K.J. McLaughlin ◽  
P. Szabo ◽  
H. Haegel ◽  
J.R. Mann
Keyword(s):  
Mouse Embryos ◽  
Chromosome 7 ◽  
Imprinted Genes ◽  
Uniparental Inheritance ◽  
Aberrant Expression ◽  
Distal Chromosome ◽  
Specific Activities ◽  
Androgenetic Embryos ◽  
Genomic Regions ◽  
Chromosome Regions

Imprinted genomic regions have been defined by the production of mice with uniparental inheritance or duplication of homologous chromosome regions. With most of the genome investigated, paternal duplication of only distal chromosomes 7 and 12 results in the lack of offspring, and prenatal lethality is presumed. Aberrant expression of imprinted genes in these two autosomal regions is therefore strongly implicated in the periimplantation lethality of androgenetic embryos. We report that mouse embryos with paternal duplication of distal chromosome 7 (PatDup.d7) die at midgestation and lack placental spongiotrophoblast. Thus, the much earlier death of androgenones must involve paternal duplication of other autosomal regions, acting independently of or synergistically with PatDup.d7. The phenotype observed is similar, if not identical to, that resulting from mutation of the imprinted distal chromosome 7 gene, Mash2, which in normal midgestation embryos exhibits spongiotrophoblast-specific maternally active/paternally inactive (m+/p-) allelic expression. Thus, the simplest explanation for the PatDup.d7 phenotype is p-/p- expression of this gene. We also confirm that PatDup.d7 embryos lack H19 RNA and posses excess Igf2 RNA as might be expected from the parental-specific activities of these genes in normal embryos.

scholarly journals ZFP57 dictates allelic expression switch of target imprinted genes

2021 ◽  
Vol 118 (5) ◽  
pp. e2005377118
Author(s):  
Weijun Jiang ◽  
Jiajia Shi ◽  
Jingjie Zhao ◽  
Qiu Wang ◽  
Dan Cong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mouse Embryos ◽  
The Other ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Imprinted Genes ◽  
Parent Of Origin

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin–dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.

scholarly journals Efficient production and transmission of CRISPR/Cas9-mediated mutant alleles at the IG-DMR via generation of mosaic mice using a modified 2CC method

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Satoshi Hara ◽  
Miho Terao ◽  
Akari Muramatsu ◽  
Shuji Takada
Keyword(s):  
Imprinted Genes ◽  
Efficient Production ◽  
Genomic Locus ◽  
Aberrant Expression ◽  
Repeat Array ◽  
Homology Directed Repair ◽  
Functional Regions ◽  
Important Approach ◽  
Imprinting Control Region ◽  
Tandem Repeat Array

AbstractGeneration of mutant imprinting control region (ICR) mice using genome editing is an important approach for elucidating ICR functions. IG-DMR is an ICR in the Dlk1-Dio3 imprinted domain that contains functional regions—in both parental alleles—that are essential for embryonic development. One drawback of this approach is that embryonic lethality can occur from aberrant expression of the imprinted genes if IG-DMR gets mutated in either the paternal or maternal allele. To overcome this problem, we generated mosaic mice that contained cells with modified IG-DMR alleles and wild-type cells using the 2CC method that allowed for microinjection of the CRISPR/Cas9 constructs into a blastomere of 2-cell embryos. This method improved the birth rate of the founder pups relative to that obtained using the standard protocol. We also successfully produced mosaic mice in which the tandem repeat array sequence in the IG-DMR had been replaced by homology directed repair. Additionally, paternal transmission of the replaced allele caused aberrant expression of the imprinted genes due to hypomethylation of the IG-DMR, indicating that the replaced allele recapitulated our deletion model. Our results indicate that this method is useful for the generation of mutant mice in which a genomic locus essential for normal development has been genetically edited.

scholarly journals The effect of superovulation on methylation and expression of imprinted genes in pre- and post-implantation mouse embryos

2007 ◽  
Vol 306 (1) ◽  
pp. 386
Author(s):  
Amanda L. Fortier ◽  
Flavia L. Lopes ◽  
Josée Martel ◽  
Jacquetta M. Trasler
Keyword(s):  
Mouse Embryos ◽  
Imprinted Genes ◽  
Post Implantation

Aberrant Expression and Methylation Status of Putatively Imprinted Genes in Placenta of Cloned Piglets

2010 ◽  
Vol 12 (2) ◽  
pp. 213-222 ◽  
Author(s):  
Yanchang Wei ◽  
Jiang Zhu ◽  
Yanjun Huan ◽  
Zhongfeng Liu ◽  
Cairong Yang ◽  
...  
Keyword(s):  
Methylation Status ◽  
Imprinted Genes ◽  
Aberrant Expression

Sodium Fluoride Affects DNA Methylation of Imprinted Genes in Mouse Early Embryos

2015 ◽  
Vol 147 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Lei Zhao ◽  
Sheng Zhang ◽  
Xinglan An ◽  
Wentao Tan ◽  
Bo Tang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Mrna Level ◽  
Mouse Embryos ◽  
Imprinted Genes ◽  
Male Mice ◽  
Early Embryos ◽  
Pregnant Mice ◽  
H19 Gene ◽  
Early Mouse

Fluorine is reported to affect embryonic development, but the underlining mechanism is unclear. The modification of DNA methylation of the H19 and Peg3 genes is important in embryonic development. Therefore, the effect of fluorine on methylation of H19 and Peg3 during early mouse embryos was studied. It was shown that the H19 gene was significantly downmethylated in E2.5, E3.5, and E4.5 embryos from pregnant mice treated with 120 mg/l NaF in drinking water for 48 h. But methylation of both H19 and Peg3 genes was disrupted when the parent male mice were treated with NaF for 35 days. H19 DNA methylation decreased significantly, while Peg3 was almost completely methylated. However, when pregnant mice, mated with NaF-treated male mice, were again treated with NaF for 48 h, either H19 or Peg3 methylation in the embryos decreased significantly. In addition, the mRNA level of H19 considerably increased in E3.5 and E4.5 embryos from NaF-treated pregnant mice. Further, the expression of DNMT1 decreased significantly after NaF treatment. Conclusively, we demonstrated that fluorine may adversely affect early embryonic development by disrupting the methylation of H19 and Peg3 through downregulation of DNMT1.

scholarly journals Molecular characterization of a congenital overgrowth syndrome induced by assisted reproduction

2017 ◽  
Author(s):  
◽  
Zhiyuan Chen
Keyword(s):  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Epigenetic Modification ◽  
Reproductive Technologies ◽  
Imprinted Genes ◽  
Aberrant Expression ◽  
Regulate Gene Expression ◽  
Loss Of Imprinting ◽  
Regulate Gene

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth condition with increased likelihood to develop childhood tumors. Children conceived with the use of assisted reproductive technologies (ART) have an increased frequency to have BWS compared to naturally conceived individuals. In ruminants, the use of ART can induce a similar overgrowth condition that phenotypically recapitulates BWS, which is referred to as large offspring syndrome (LOS). It is believed that these two overgrowth conditions are the result of misregulation of a set of genes that are expressed only from the maternally- or paternally-inherited chromosomes. These genes are known as imprinted genes. In this dissertation, we demonstrate that multiple imprinted genes are misregulated in LOS, as in a subset of BWS. Further, we show that global misregulation of non-imprinted genes in addition to loss-of-imprinting characterizes LOS. Importantly, most of the genes with aberrant expression are not associated with differential DNA methylation, an epigenetic modification that can regulate gene expression. Our results lay the foundation to predict the occurrence of LOS and help understand the molecular mechanisms of these congenital overgrowth conditions.

scholarly journals Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats

Reproduction ◽  
2013 ◽  
Vol 146 (2) ◽  
pp. 155-168 ◽  
Author(s):  
Neelam A Kedia-Mokashi ◽  
Leena Kadam ◽  
Mandar Ankolkar ◽  
Kushaan Dumasia ◽  
N H Balasinor
Keyword(s):  
De Novo ◽  
Methylation Status ◽  
Cpg Islands ◽  
Transcript Level ◽  
Male Rats ◽  
Imprinted Genes ◽  
Aberrant Methylation ◽  
Aberrant Expression ◽  
Treated Male ◽  
Epigenetic Phenomenon

Genomic imprinting is an epigenetic phenomenon known to regulate fetal growth and development. Studies from our laboratory have demonstrated that treatment of adult male rats with tamoxifen increased postimplantation loss around mid gestation. Further studies demonstrated the aberrant expression of transcripts of several imprinted genes in the resorbing embryos at days 11 and 13 of gestation including IGF2. In addition, decreased methylation at theIgf2–H19imprint control region was observed in spermatozoa and in resorbing embryos sired by tamoxifen-treated males. In this study, methylation analysis of the imprinted genes, which were found to be differentially expressed, was done using EpiTYPER in the spermatozoa of tamoxifen-treated rats and in postimplantation embryos sired by tamoxifen-treated rats. Differentially methylated regions (DMRs) for most imprinted genes have not been identified in the rats. Hence, initial experiments were performed to identify the putative DMRs in the genes selected for the study. Increased methylation at CpG islands present in the putative DMRs of a number of imprinted genes was observed in the resorbing embryos sired by tamoxifen-treated male rats. This increase in methylation is associated with the downregulation of most of these genes at the transcript level in resorbing embryos. No change in the methylation status of these genes was observed in spermatozoa. These observations suggest that a deregulation of mechanisms protecting unmethylated alleles from a wave ofde novomethylation occurs following implantation.

Aberrant expression of imprinted genes and their regulatory network in cloned cattle

2012 ◽  
Vol 78 (4) ◽  
pp. 858-866 ◽  
Author(s):  
Z.-J. Gong ◽  
Y.-Y. Zhou ◽  
M. Xu ◽  
Q. Cai ◽  
H. Li ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Imprinted Genes ◽  
Aberrant Expression

Aberrant expression of miR‐29a/29b and methylation level of mouse embryos after in vitro fertilization and vitrification at two‐cell stage

2019 ◽  
Vol 234 (10) ◽  
pp. 18942-18950 ◽  
Author(s):  
Elham Movahed ◽  
Mansooreh Soleimani ◽  
Sara Hosseini ◽  
Azade Akbari Sene ◽  
Mohammad Salehi
Keyword(s):  
In Vitro Fertilization ◽  
Methylation Level ◽  
Mouse Embryos ◽  
Cell Stage ◽  
Aberrant Expression ◽  
Vitro Fertilization
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