scholarly journals Transient Reduction of DNA Methylation at the Onset of Meiosis in Male Mice

2017 ◽  
Author(s):  
Valeriya Gaysinskaya ◽  
Brendan F. Miller ◽  
Godfried W. van der Heijden ◽  
Kasper D. Hansen ◽  
Alex Bortvin
Keyword(s):  
Dna Methylation ◽  
Quality Control ◽  
Germ Cells ◽  
Extended Period ◽  
S Phase ◽  
Male Mice ◽  
Wild Type ◽  
Genome Wide ◽  
Wild Type Male

AbstractThe quality of germ cells depends on successful chromatin organization in meiotic prophase I (MPI). To better understand the epigenetic context of MPI we studied the dynamics of DNA methylation in wild-type male mice. We discovered an extended period of genome-wide transient reduction of DNA methylation (TRDM) during early MPI. Our data show that TRDM arises by passive demethylation in the premeiotic S phase highlighting the abundance of hemimethylated DNA in MPI. Importantly, TRDM unmasks a deficit in retrotransposon LINE-1 DNA methylation contributing to its expression in early MPI. We propose that TRDM facilitates meiosis and gamete quality control.

Dysregulation of schizophrenia-associated genes and genome-wide hypomethylation in neurons overexpressing DNMT1

Epigenomics ◽  
2021 ◽  
Author(s):  
Sonal Saxena ◽  
Sumana Choudhury ◽  
Pranay Amruth Maroju ◽  
Anuhya Anne ◽  
Lov Kumar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Copy Number ◽  
Embryonic Stem ◽  
Wild Type ◽  
Independent Manner ◽  
Transcript Levels ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Increased Activity

Aim: To study the effects of DNMT1 overexpression on transcript levels of genes dysregulated in schizophrenia and on genome-wide methylation patterns. Materials & methods: Transcriptome and DNA methylome comparisons were made between R1 (wild-type) and Dnmt1tet/tet mouse embryonic stem cells and neurons overexpressing DNMT1. Genes dysregulated in both Dnmt1tet/tet cells and schizophrenia patients were studied further. Results & conclusions: About 50% of dysregulated genes in patients also showed altered transcript levels in Tet/Tet neurons in a DNA methylation-independent manner. These neurons unexpectedly showed genome-wide hypomethylation, increased transcript levels of Tet1 and Apobec 1-3 genes and increased activity and copy number of LINE-1 elements. The observed similarities between Tet/Tet neurons and schizophrenia brain samples reinforce DNMT1 overexpression as a risk factor.

scholarly journals Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 372
Author(s):  
Daiki Aomura ◽  
Makoto Harada ◽  
Yosuke Yamada ◽  
Takero Nakajima ◽  
Koji Hashimoto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Male Mice ◽  
Histological Findings ◽  
Tubular Injury ◽  
Wild Type ◽  
Wild Type Male ◽  
And Oxidative Stress

As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.

scholarly journals The Importance of Quality Control of LSDV Live Attenuated Vaccines for Its Safe Application in the Field

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1019
Author(s):  
Andy Haegeman ◽  
Ilse De Leeuw ◽  
Meruyert Saduakassova ◽  
Willem Van Campe ◽  
Laetitia Aerts ◽  
...  
Keyword(s):  
Quality Control ◽  
Skin Disease ◽  
Wild Type ◽  
Lumpy Skin Disease ◽  
Pcr Screening ◽  
Live Attenuated Vaccines ◽  
Goatpox Virus ◽  
The Impact

Vaccination is an effective approach to prevent, control and eradicate diseases, including lumpy skin disease (LSD). One of the measures to address farmer hesitation to vaccinate is guaranteeing the quality of vaccine batches. The purpose of this study was to demonstrate the importance of a quality procedure via the evaluation of the LSD vaccine, Lumpivax (Kevevapi). The initial PCR screening revealed the presence of wild type LSD virus (LSDV) and goatpox virus (GTPV), in addition to vaccine LSDV. New phylogenetic PCRs were developed to characterize in detail the genomic content and a vaccination/challenge trial was conducted to evaluate the impact on efficacy and diagnostics. The characterization confirmed the presence of LSDV wild-, vaccine- and GTPV-like sequences in the vaccine vial and also in samples taken from the vaccinated animals. The analysis was also suggestive for the presence of GTPV-LSDV (vaccine/wild) recombinants. In addition, the LSDV status of some of the animal samples was greatly influenced by the differentiating real-PCR used and could result in misinterpretation. Although the vaccine was clinically protective, the viral genomic content of the vaccine (being it multiple Capripox viruses and/or recombinants) and the impact on the diagnostics casts serious doubts of its use in the field.

scholarly journals Genome-Wide DNA Methylation Analysis Reveals Epigenetic Dysregulation of MicroRNA-34A in TP53-Associated Cancer Susceptibility

2016 ◽  
Vol 34 (30) ◽  
pp. 3697-3704 ◽  
Author(s):  
Nardin Samuel ◽  
Gavin Wilson ◽  
Mathieu Lemire ◽  
Badr Id Said ◽  
Youliang Lou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Peripheral Blood ◽  
Tp53 Mutation ◽  
Cancer Predisposition ◽  
Wild Type ◽  
Primary Tumors ◽  
Bisulfite Pyrosequencing ◽  
Tp53 Mutations ◽  
Mutation Carriers ◽  
Genome Wide

Purpose Although the link between mutant TP53 and human cancer is unequivocal, a significant knowledge gap exists in clinically actionable molecular targets in Li-Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with germline mutations in TP53. This study surveyed the epigenome to identify functionally and clinically relevant novel genes implicated in LFS. Patients and Methods We performed genome-wide methylation analyses of peripheral blood leukocyte DNA in germline TP53 mutation carriers (n = 72) and individuals with TP53 wild type in whom histologically comparable malignancies developed (n = 111). Targeted bisulfite pyrosequencing was performed on a validation cohort of 30 TP53 mutation carriers and 46 patients with TP53 wild type, and candidate sites were evaluated in primary tumors from patients with LFS across multiple histologic tumor types. Results In 183 patients, distinct DNA methylation signatures were associated with deleterious TP53 mutations in peripheral blood leukocytes. TP53-associated DNA methylation marks occurred in genomic regions that harbored p53 binding sites and in genes encoding p53 pathway proteins. Moreover, loss-of-function TP53 mutations were significantly associated with differential methylation at the locus encoding microRNA miR-34A, a key component of the p53 regulatory network (adjusted P < .001), and validated in an independent patient cohort (n = 76, P < .001). Targeted bisulfite pyrosequencing demonstrated that miR-34A was inactivated by hypermethylation across many histologic types of primary tumors from patients with LFS. Moreover, miR-34A tumor hypermethylation was associated with decreased overall survival in a cohort of 29 patients with choroid plexus carcinomas, a characteristic LFS tumor (P < .05). Conclusion Epigenetic dysregulation of miR-34A may comprise an important path in TP53-associated cancer predisposition and represents a therapeutically actionable target with potential clinical relevance.

scholarly journals Gender- and Age-dependent Changes in Kidney Androgen Protein mRNA Expression in a Knockout Mouse Model for Nephrolithiasis

2002 ◽  
Vol 50 (12) ◽  
pp. 1663-1669 ◽  
Author(s):  
Eleni G. Tzortzaki ◽  
Dayna Glass ◽  
Min Yang ◽  
Andrew P. Evan ◽  
Sharon B. Bledsoe ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Kidney Tissue ◽  
Mouse Kidney ◽  
Male Mice ◽  
Wild Type ◽  
Rt Pcr ◽  
Cytoplasmic Staining ◽  
Female Mice ◽  
Age Dependent ◽  
Wild Type Male

Kidney androgen-regulated protein (Kap) is the most abundant protein in the mouse kidney, but its function is unknown. We previously observed a significant decrease in Kap mRNA expression in whole kidney tissue from male mice with adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadenine (DHA) nephrolithiasis. The disease phenotype is more severe in male mice and is age-dependent. To identify the cellular basis for differential Kap expression, we used in situ hybridization (ISH) and reverse transcription-polymerase chain reaction ISH (RT-PCR ISH) to identify the cell types expressing this mRNA in paraffin-embedded kidney sections. In 1-month-old wild-type male mice, Kap was detected primarily in S3 proximal tubule segments, but expression was very low in female mice. In 1-month-old APRT-deficient male mice, Kap expression was decreased significantly and was undetectable in female mice. Kap mRNA was not detected in 3- or 6-month-old mice using our standard ISH protocol, but we observed intense cytoplasmic staining in S3 proximal tubules in wild-type male mice of these age groups using an improved RT-PCR ISH procedure. Our studies demonstrate age-, gender-, and APRT genotype-dependent changes in Kap mRNA expression in mouse kidney. Kap expression is under multihormonal control, and hormonal changes in DHA-induced nephrolithiasis may account for the decreased Kap expression in APRT-deficient mice.

scholarly journals Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells

2007 ◽  
Vol 307 (2) ◽  
pp. 368-379 ◽  
Author(s):  
C.C. Oakes ◽  
S. La Salle ◽  
D.J. Smiraglia ◽  
B. Robaire ◽  
J.M. Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cells ◽  
Male Germ Cells ◽  
Genome Wide

Aging Cartilage in Wild-Type Mice: An Observational Study

Cartilage ◽  
2020 ◽  
pp. 194760352092671
Author(s):  
Joulnar Akoum ◽  
Khadija Tahiri ◽  
Marie-Thérèse Corvol ◽  
Didier Borderie ◽  
François Étienne ◽  
...  
Keyword(s):  
Walking Speed ◽  
Articular Surface ◽  
Type Ii Collagen ◽  
Research Society ◽  
Male Mice ◽  
Wild Type ◽  
Calcified Cartilage ◽  
Age Related ◽  
Wild Type Male ◽  
Osteoarthritis Research Society

Objective To describe the spontaneous evolution of age-related changes affecting knee joint articular cartilage, walking speed and a serum biomarker of cartilage remodeling in C57BL/6-JRj wild-type male mice. Design Histological changes were assessed by the Osteoarthritis Research Society International (OARSI) score (0=normal, 6=vertical clefts/erosion to the calcified cartilage extending >75% of the articular surface) in newborn, 1-week- and 1-, 3-, 6-, 9- and 12-month-old C57BL/6-JRj wild-type male mice, walking speed by the Locotronic system, and serum C-terminal telopeptide of type II collagen (CTX-II) content by ELISA in 1-, 3-, 6-, and 9-month-old C57BL/6-JRj wild-type male mice. Results Mean (SD) OARSI score significantly increased from 0.2 (0.3) to 1.3 (0.6) ( p=0.03) between 1 and 3 months of age and from 1.3 (0.6) to 3.3 (0.6) ( p=0.04) between 3 and 6 months of age. Mean walking speed was stable between 1 and 6 months of age but significantly decreased from 11.4 (1.8) to 3.2 (0.8) cm.s-1 ( p=0.03) between 6 and 9 months of age. Serum CTX-II content was maximal at 1 month of age, then decreased from 12.2 (8.5) to 2.4 (8.4) pg/ml ( p=0.02) between 1 and 3 months of age, remaining low and stable thereafter. Conclusions C57BL/6-JRj wild-type male mice showed continuously increasing osteoarthritic changes but delayed decreasing walking speed with age. These variations were maximal between 3 and 9 months of age. Maximal serum CTX-II content preceded these changes.

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