scholarly journals Multiomic profiling of the liver across diets and age in a diverse mouse population

Cell Systems ◽  
2021 ◽  
Author(s):  
Evan G. Williams ◽  
Niklas Pfister ◽  
Suheeta Roy ◽  
Cyril Statzer ◽  
Jack Haverty ◽  
...  
Keyword(s):  
Mouse Population

scholarly journals A system for automatic recording of social behavior in a free-living wild house mouse population

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Barbara König ◽  
Anna K. Lindholm ◽  
Patricia C. Lopes ◽  
Akos Dobay ◽  
Sally Steinert ◽  
...  
Keyword(s):  
Social Behavior ◽  
House Mouse ◽  
Automatic Recording ◽  
Free Living ◽  
Mouse Population ◽  
Wild House Mouse

scholarly journals Three-locus and four-locus QTL interactions influence mouse insulin-like growth factor-I

2006 ◽  
Vol 26 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Philip Hanlon ◽  
William Andrew Lorenz ◽  
Zhihong Shao ◽  
James M. Harper ◽  
Andrzej T. Galecki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Serum Insulin ◽  
Genome Scan ◽  
Chromosome 17 ◽  
Insulin Like Growth Factor ◽  
Mouse Population ◽  
Factor I ◽  
A Genome ◽  
Igf I ◽  
Growth Factor I

A previous analysis of serum insulin-like growth factor I (IGF-I) levels in a mouse population ( n = 961) derived from a cross of (BALB/cJ × C57BL/6J) F1 females and (C3H/HeJ × DBA/2J) F1 males documented quantitative trait loci (QTL) on chromosomes 1, 10, and 17. We employed a newly developed, random walk-based method to search for three- and four-way allelic combinations that might influence IGF-I levels through nonadditive (conditional or epistatic) interactions among 185 genotyped biallelic loci and with significance defined by experiment-wide permutation ( P < 0.05). We documented a three-locus combination in which an epistatic interaction between QTL on paternal-derived chromosomes 5 and 18 had an opposite effect on the phenotype based on the allele inherited at a third locus on maternal-derived chromosome 17. The search also revealed three four-locus combinations that influence IGF-I levels through nonadditive genetic interactions. In two cases, the four-allele combinations were associated with animals having high levels of IGF-I, and, in the third case, a four-allele combination was associated with animals having low IGF-I levels. The multiple-locus genome scan algorithm revealed new IGF-I QTL on chromosomes 2, 4, 5, 7, 8, and 12 that had not been detected in the single-locus genome search and showed that levels of this hormone can be regulated by complex, nonadditive interactions among multiple loci. The analysis method can detect multilocus interactions in a genome scan experiment and may provide new ways to explore the genetic architecture of complex physiological phenotypes.

scholarly journals Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 1942-1952 ◽  
Author(s):  
Pin Wang ◽  
Yunshan Wang ◽  
Sasha A Langley ◽  
Yan-Xia Zhou ◽  
Kuang-Yu Jen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Model ◽  
Rna Sequencing ◽  
Genetic Association ◽  
Association Analysis ◽  
Collaborative Cross ◽  
Sequencing Analysis ◽  
Genetic Association Analysis ◽  
Mouse Population ◽  
Wide Range

ObjectiveThe Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum.DesignWe monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of ISG15 by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis.ResultsCC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified Nfκb1 as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS.ConclusionsCC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.

scholarly journals The role of host phenology for parasite transmission

2020 ◽  
Author(s):  
Hannelore MacDonald ◽  
Erol Akçay ◽  
Dustin Brisson
Keyword(s):  
Species Interactions ◽  
Activity Period ◽  
Parasite Transmission ◽  
Nymphal Stage ◽  
Mouse Population ◽  
Tick Activity ◽  
Contact Rates ◽  
Wide Range ◽  
Host Phenology ◽  
Host Parasite

Abstract Phenology is a fundamental determinant of species distributions, abundances, and interactions. In host–parasite interactions, host phenology can affect parasite fitness due to the temporal constraints it imposes on host contact rates. However, it remains unclear how parasite transmission is shaped by the wide range of phenological patterns observed in nature. We develop a mathematical model of the Lyme disease system to study the consequences of differential tick developmental-stage phenology for the transmission of B. burgdorferi. Incorporating seasonal tick activity can increase B. burgdorferi fitness compared to continuous tick activity but can also prevent transmission completely. B. burgdorferi fitness is greatest when the activity period of the infectious nymphal stage slightly precedes the larval activity period. Surprisingly, B. burgdorferi is eradicated if the larval activity period begins long after the end of nymphal activity due to a feedback with mouse population dynamics. These results highlight the importance of phenology, a common driver of species interactions, for the fitness of a parasite.

scholarly journals Nitrosative Stress and Lipid Homeostasis as a Mechanism for Zileuton Hepatotoxicity and Resistance in Genetically Sensitive Mice

2020 ◽  
Vol 175 (2) ◽  
pp. 220-235 ◽  
Author(s):  
Dahea You ◽  
Lascelles E Lyn-Cook ◽  
Daniel M Gatti ◽  
Natalie Bell ◽  
Philip R Mayeux ◽  
...  
Keyword(s):  
Liver Injury ◽  
Nitrosative Stress ◽  
Farnesoid X Receptor ◽  
Therapeutic Interventions ◽  
Mechanistic Study ◽  
Acid Oxidation ◽  
Fatty Change ◽  
Active Inhibitor ◽  
Mouse Population ◽  
Mechanisms Of Toxicity

Abstract Zileuton is an orally active inhibitor of leukotriene synthesis for maintenance treatment of asthma, for which clinical usage has been associated with idiosyncratic liver injury. Mechanistic understanding of zileuton toxicity is hampered by the rarity of the cases and lack of an animal model. A promising model for mechanistic study of rare liver injury is the Diversity Outbred (J:DO) mouse population, with genetic variation similar to that found in humans. In this study, female DO mice were administered zileuton or vehicle daily for 7 days (i.g.). Serum liver enzymes were elevated in the zileuton group, with marked interindividual variability in response. Zileuton exposure-induced findings in susceptible DO mice included microvesicular fatty change, hepatocellular mitosis, and hepatocellular necrosis. Inducible nitric oxide synthase and nitrotyrosine abundance were increased in livers of animals with necrosis and those with fatty change, implicating nitrosative stress as a possible injury mechanism. Conversely, DO mice lacking adverse liver pathology following zileuton exposure experienced decreased hepatic concentrations of resistin and increased concentrations of insulin and leptin, providing potential clues into mechanisms of toxicity resistance. Transcriptome pathway analysis highlighted mitochondrial dysfunction and altered fatty acid oxidation as key molecular perturbations associated with zileuton exposure, and suggested that interindividual differences in cytochrome P450 metabolism, glutathione-mediated detoxification, and farnesoid X receptor signaling may contribute to zileuton-induced liver injury (ZILI). Taken together, DO mice provided a platform for investigating mechanisms of toxicity and resistance in context of ZILI which may lead to targeted therapeutic interventions.

scholarly journals Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans

2009 ◽  
Vol 19 (9) ◽  
pp. 1507-1515 ◽  
Author(s):  
A. H. Harrill ◽  
P. B. Watkins ◽  
S. Su ◽  
P. K. Ross ◽  
D. E. Harbourt ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Population

The effect of increased ground-level habitat complexity on mouse population dynamics

2003 ◽  
Vol 30 (6) ◽  
pp. 565 ◽  
Author(s):  
A. D. Arthur ◽  
R. P. Pech ◽  
A. Drew ◽  
E. Gifford ◽  
S. Henry ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Native Species ◽  
Habitat Complexity ◽  
Habitat Structure ◽  
Ground Level ◽  
Low Complexity ◽  
Mouse Population ◽  
Introduced Predators ◽  
The Impact

We investigated experimentally the influence of habitat structure on the population dynamics of house mice. Three habitat types were used. In one, dense stands of regenerating cypress pine were felled and left in situ to cover at least 40% of experimental plots, providing high complexity at ground level; in another, dense stands of regenerating pine were left intact, providing low complexity at ground level; in the third, open grassland adjacent to dense stands of regenerating pine also provided low complexity at ground level. Mouse populations occurred at higher densities in felled pine plots compared with both the standing pine and grassland plots, consistent with the hypothesis that the presence of increased habitat complexity at ground level reduced the impact of predation. Even though populations responded to the felled pine, they dropped to very low densities over winter, suggesting that the habitat was still marginal for the persistence of mice, probably due to a lack of food. The results are discussed with reference to their implications for the influence that habitat structure may have on the impact of introduced predators on native species.

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