scholarly journals Body weight at young adulthood and association with epigenetic aging and lifespan in the BXD murine family

2019 ◽  
Author(s):  
Jose Vladimir Sandoval-Sierra ◽  
Alexandra H. B. Helbing ◽  
Evan G. Williams ◽  
David G. Ashbrook ◽  
Suheeta Roy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Young Adulthood ◽  
Inbred Mouse ◽  
Accelerated Aging ◽  
Mouse Strains ◽  
Epigenetic Clock ◽  
Epigenetic Aging ◽  
Normal Chow ◽  
Average Methylation

SummaryDNA methylation (DNAm) is shaped by genetic and environmental factors and modulated by aging. Here, we examine interrelations between epigenetic aging, body weight (BW), and lifespan in 12 inbred mouse strains from the BXD panel that exhibit over two-fold variation in longevity. Genome-wide DNAm was assayed in 70 liver specimens from mice ranging in age from 6 to 25 months that were maintained on normal chow or high fat diet (HFD). We defined subsets of CpG regions associated with age, BW at young adulthood, and strain-by-diet dependent life expectancy. The age associated differentially methylated CpG regions (age-DMRs) featured distinct genomic characteristics, with DNAm gains over time occurring in sites with high CpG density and low average methylation. CpG regions associated with BW were enriched in introns and generally showed lower methylation in mice with higher BW, and inversely correlated with gene expression such that mRNA was higher in mice with higher BW. Lifespan-associated regions featured no distinct genomic characteristics but were linked to genes involved in lifespan regulation, including the telomerase reverse transcriptase gene, Tert, which showed lower methylation and higher gene expression in long-lived strains. An epigenetic clock defined from the age-DMRs conveyed accelerated aging in mice belonging to strains with shorter lifespans. Both higher BW at young adulthood and HFD were associated with accelerated epigenetic aging. Our results highlight the age-accelerating effect of heavier body weight. Furthermore, the study demonstrates that the measure of epigenetic aging derived from age-DMRs can predict strain and diet-induced differences in lifespan.

scholarly journals The relationship between nephron number, kidney size and body weight in two inbred mouse strains

Organogenesis ◽  
2010 ◽  
Vol 6 (3) ◽  
pp. 189-194 ◽  
Author(s):  
Inga J. Murawski ◽  
Rita W. Maina ◽  
Indra R. Gupta
Keyword(s):  
Body Weight ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Nephron Number ◽  
Kidney Size ◽  
The Relationship

Abstract 268: Strain-specific Cardiac Fibroblast Response to Isoproterenol-induced Cardiac Fibrosis

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shuin Park ◽  
Sara Ranjbarvaziri ◽  
Fides Lay ◽  
Peng Zhao ◽  
Aldons J Lusis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Expression Profiles ◽  
Inbred Mouse ◽  
Gene Expression Profiles ◽  
Mouse Strains ◽  
Sequencing Analysis ◽  
Different Strains

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.

Cis -acting regulation of splenic Art2 gene expression in inbred mouse strains

1999 ◽  
Vol 49 (7-8) ◽  
pp. 700-703 ◽  
Author(s):  
Deborah F. Sardinha ◽  
Thiruchandurai V. Rajan
Keyword(s):  
Gene Expression ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Cis Acting

Integrative analysis reveals mouse strain-dependent responses to acute ozone exposure associated with airway macrophage transcriptional activity

2021 ◽  
Author(s):  
Adelaide Tovar ◽  
Wesley L. Crouse ◽  
Gregory J. Smith ◽  
Joseph M. Thomas ◽  
Benjamin P. Keith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Inbred Mouse ◽  
Chromatin Accessibility ◽  
Ozone Exposure ◽  
Mouse Strains ◽  
Human Populations ◽  
Transcriptional Responses ◽  
Adult Mice ◽  
Strain Dependent

Acute ozone (O3) exposure is associated with multiple adverse cardiorespiratory outcomes, the severity of which varies across individuals in human populations and inbred mouse strains. However, molecular determinants of response, including susceptibility biomarkers that distinguish who will develop severe injury and inflammation, are not well characterized. We and others have demonstrated that airway macrophages (AMs) are an important resident immune cell type that are functionally and transcriptionally responsive to O3 inhalation. Here, we sought to explore influences of strain, exposure, and strain-by-O3 exposure interactions on AM gene expression and identify transcriptional correlates of O3-induced inflammation and injury across 6 mouse strains, including 5 Collaborative Cross (CC) strains. We exposed adult mice of both sexes to filtered air (FA) or 2 ppm O3 for 3 hours, and measured inflammatory and injury parameters 21 hours later. Mice exposed to O3 developed airway neutrophilia and lung injury with strain-dependent severity. In AMs, we identified a common core O3 response signature across all strains, as well as a set of genes exhibiting strain-by-O3 exposure interactions. In particular, a prominent gene expression contrast emerged between a low- (CC017/Unc) and high-responding (CC003/Unc) strain, as reflected by cellular inflammation and injury. Further inspection indicated that differences in their baseline gene expression and chromatin accessibility profiles likely contributes to their divergent post-O3 exposure transcriptional responses. Together, these results suggest that aspects of O3-induced respiratory responses are mediated through altered AM transcriptional signatures, and further confirms the importance of gene-environment interactions in mediating differential responsiveness to environmental agents.

The B4galnt2 Regulatory Polymorphism, Mvwf1, Causes Low VWF Levels and Segregates in Natural Mouse Populations

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 542-542
Author(s):  
Jill Johnsen ◽  
John Baines ◽  
Diethard Tautz ◽  
David Ginsburg
Keyword(s):  
Gene Expression ◽  
Central Region ◽  
Haplotype Block ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Regulatory Mutation ◽  
Wild Mice ◽  
Massif Central ◽  
Tissue Specific

Abstract We previously identified the cause of low levels of von Willebrand factor (VWF) in the RIIIS/J mouse strain to be a regulatory mutation, Mvwf1, in an N-acetylgalactosaminyltransferase, B4galnt2 (previously designated Galgt2). Mvwf1 causes a tissue-specific switch in B4galnt2 expression from intestinal epithelium to vascular endothelium, resulting in aberrant glycosylation of VWF and accelerated clearance from circulation. We have identified thirteen Mvwf1 inbred mouse strains that share this remarkable tissue-specific switch and a common 97kb haplotype block, including a 30kb region of 2–3% sequence divergence that flanks Exon 1. An RIIIS/J BAC transgene containing the entire Mvwf1 haplotype block and B4galnt2 gene confers vascular gene expression, while C57BL6/J BAC transgenes spanning the homologous region confer “wild-type” vessel(−), intestine(+) gene expression, indicating that one or more tissue-specific regulatory elements sufficient to recapitulate the Mvwf1 tissue-specific switch lie within the genomic region covered by these BACs. A wild-derived recombinant Mvwf1 allele containing the 3′ half of the Mvwf1 haplotype block confers the vessel(−), intestine(+) B4galnt2 expression pattern, placing the regulatory mutation(s) responsible for the Mvwf1 switch well upstream of the proximal promoter region. Sequence analysis of DNA from wild-caught individual mice confirmed the presence of a highly conserved wild mouse Mvwf1 founder allele that likely pre-dates the development of the inbred mouse strains. PCR of genomic DNA from wild caught mice representing M. m. musculus, M. m. domesticus, M. m. castaneus, M. m. molossinus, M. spretus, M. hortulanis, and M. macedonicus revealed that the Mvwf1 allele is common in wild M. m. domesticus populations in North America, Europe, and Africa, with an allele frequency as high as 60% in French mice. Population samples of M. m. domesticus from Cologne, Germany and the Massif Central region of France drastically differ in the frequency of this allele (0% vs. 60%). A significant reduction in microsatellite variability at B4galnt2 in the French population, as measured by the lnRH statistic, suggests a recent, local shift in the frequency of Mvwf1, likely due to a recent change in selective pressure. Analysis of independently trapped wild mice from the Massif Central region of France confirmed that Mvwf1 confers vascular endothelial B4galnt2 expression and causes significantly lower VWF levels (5.5+2.0 vs. 13.3+2.3, p<1x10−7) in this population. These data support a B4Galnt2 allele-specific survival advantage in wild mice, leading us to speculate that a similar survival advantage could account for the high prevalence of VWD in human populations.

scholarly journals Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains

2014 ◽  
Vol 193 (9) ◽  
pp. 4485-4496 ◽  
Author(s):  
Sara Mostafavi ◽  
Adriana Ortiz-Lopez ◽  
Molly A. Bogue ◽  
Kimie Hattori ◽  
Cristina Pop ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Control ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Control Of Gene Expression
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