scholarly journals Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice

2018 ◽  
Author(s):  
Guanglin Zhang ◽  
Hyae Ran Byun ◽  
Zhe Ying ◽  
Montgomery Blencowe ◽  
Yuqi Zhao ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Individual Variability ◽  
Mouse Strains ◽  
Fructose Intake ◽  
Cholesterol Levels ◽  
High Fructose ◽  
Ppar Signaling ◽  
Gene Regulatory ◽  
Metabolic Dysfunctions ◽  
Distinct Features

AbstractHigh fructose intake is a major risk for metabolic syndrome; however, its effects seem to vary across individuals. To determine main factors involved in the inter-individual responses to fructose, we fed inbred mouse strains C57BL/6J (B6), DBA/2J (DBA) and FVB/NJ (FVB) with fructose. DBA mice showed the highest susceptibility to gain adiposity and glucose intolerance. Elevated insulin was found in DBA and FVB mice, and cholesterol levels were uniquely elevated in B6 mice. The transcriptional profiles of liver, hypothalamus, and adipose tissues showed strain- and tissue-specific pathways altered by fructose, such as fatty acid and cholesterol pathways for B6 and PPAR signaling for DBA in liver, and oxidative phosphorylation for B6 and protein processing for DBA in hypothalamus. Using network modeling, we predicted potential strain-specific key regulators of fructose response such as Fgf21 (DBA) and Lss (B6) in liver, and validated strain-biased responses as well as the regulatory actions of Fgf21 and Lss in primary hepatocytes. Our findings support that fructose perturbs individualized tissue networks and pathways and associates with distinct features of metabolic dysfunctions across genetically diverse mice. Our results elucidate the molecular pathways and gene regulatory mechanisms underlying inter-individual variability in response to high fructose diet.

scholarly journals N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 442
Author(s):  
Gunn-Guang Liou ◽  
Cheng-Chi Hsieh ◽  
Yi-Ju Lee ◽  
Pin-Hung Li ◽  
Ming-Shiun Tsai ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Serum Triglyceride ◽  
Mouse Strains ◽  
High Dose ◽  
Therapeutic Effects ◽  
Protein Nitration ◽  
Cholesterol Levels ◽  
Antioxidative Enzyme Activities ◽  
Acetyl Cysteine ◽  
Dose Dependent

Acetaminophen (APAP) overdose induces acute liver damage and even death. The standard therapeutic dose of N-acetyl cysteine (NAC) cannot be applied to every patient, especially those with high-dose APAP poisoning. There is insufficient evidence to prove that increasing NAC dose can treat patients who failed in standard treatment. This study explores the toxicity of NAC overdose in both APAP poisoning and normal mice. Two inbred mouse strains with different sensitivities to propacetamol-induced hepatotoxicity (PIH) were treated with different NAC doses. NAC therapy decreased PIH by reducing lipid oxidation, protein nitration and inflammation, and increasing glutathione (GSH) levels and antioxidative enzyme activities. However, the therapeutic effects of NAC on PIH were dose-dependent from 125 (N125) to 275 mg/kg (N275). Elevated doses of NAC (400 and 800 mg/kg, N400 and N800) caused additional deaths in both propacetamol-treated and normal mice. N800 treatments significantly decreased hepatic GSH levels and induced inflammatory cytokines and hepatic microvesicular steatosis in both propacetamol-treated and normal mice. Furthermore, both N275 and N400 treatments decreased serum triglyceride (TG) and induced hepatic TG, whereas N800 treatment significantly increased interleukin-6, hepatic TG, and total cholesterol levels. In conclusion, NAC overdose induces hepatic and systemic inflammations and interferes with fatty acid metabolism.

scholarly journals QTL mapping for genetic determinants of lipoprotein cholesterol levels in combined crosses of inbred mouse strains,

2006 ◽  
Vol 47 (8) ◽  
pp. 1780-1790 ◽  
Author(s):  
Henning Wittenburg ◽  
Malcolm A. Lyons ◽  
Renhua Li ◽  
Ulrike Kurtz ◽  
Xiaosong Wang ◽  
...  
Keyword(s):  
Qtl Mapping ◽  
Inbred Mouse ◽  
Lipoprotein Cholesterol ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Genetic Determinants ◽  
Cholesterol Levels

scholarly journals Pituitary Tumor Transforming Gene 1 orchestrates gene regulatory variation in mouse ventral midbrain during aging

2020 ◽  
Author(s):  
Yujuan Gui ◽  
Mélanie H. Thomas ◽  
Pierre Garcia ◽  
Mona Karout ◽  
Rashi Halder ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dopaminergic Neurons ◽  
Inbred Mouse ◽  
Differentially Expressed ◽  
Molecular Networks ◽  
Mouse Strains ◽  
Rna Seq ◽  
Regulatory Variation ◽  
Ventral Midbrain ◽  
Gene Regulatory

AbstractBackgroundDopaminergic neurons in the midbrain are of particular interest due to their role in diseases such as Parkinson’s disease and schizophrenia. Genetic variation between individuals can affect the integrity and function of dopaminergic neurons but the DNA variants and molecular cascades modulating dopaminergic neurons and other cells types of ventral midbrain remain poorly defined. Three genetically diverse inbred mouse strains — C57BL/6J, A/J, and DBA/2J — differ significantly in their genomes (~7 million variants), motor and cognitive behavior, and susceptibility to neurotoxins.ResultsTo further dissect the underlying molecular networks responsible for these variable phenotypes, we generated RNA-seq and ChIP-seq data from ventral midbrains of the 3 mouse strains. We defined 1000–1200 transcripts that are differentially expressed among them. These widespread differences may be due to altered activity or expression of upstream transcription factors. Interestingly, transcription factors were significantly underrepresented among the differentially expressed genes, and only one TF, Pttg1, showed significant differences among all strains. The changes in Pttg1 expression were accompanied by consistent alterations in histone H3 lysine 4 trimethylation at Pttg1 transcription start site. The ventral midbrain transcriptome of three-month-old C57BL/6J congenic Pttg1-/- mutants was only modestly altered, but shifted towards that of A/J and DBA/2J in nine-month-old mice. Principle component analysis identified the genes underlying the transcriptome shift and deconvolution of these bulk RNA-seq changes using midbrain single cell RNA-seq data suggested that the changes were occurring in several different cell types, including neurons, oligodendrocytes, and astrocytes.ConclusionTaken together, our results show that Pttg1 contributes to gene regulatory variation between mouse strains and influences mouse midbrain transcriptome during aging.

scholarly journals Genetic Control of Mammalian Meiotic Recombination. I. Variation in Exchange Frequencies Among Males From Inbred Mouse Strains

Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 297-306 ◽  
Author(s):  
Kara E Koehler ◽  
Jonathan P Cherry ◽  
Audrey Lynn ◽  
Patricia A Hunt ◽  
Terry J Hassold
Keyword(s):  
Meiotic Recombination ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Male Meiosis ◽  
Mouse Strains ◽  
Recombination Rates ◽  
The Mean ◽  
Genetic Background Effects ◽  
Exchange Patterns ◽  
Positive Interference

AbstractGenetic background effects on the frequency of meiotic recombination have long been suspected in mice but never demonstrated in a systematic manner, especially in inbred strains. We used a recently described immunostaining technique to assess meiotic exchange patterns in male mice. We found that among four different inbred strains—CAST/Ei, A/J, C57BL/6, and SPRET/Ei—the mean number of meiotic exchanges per cell and, thus, the recombination rates in these genetic backgrounds were significantly different. These frequencies ranged from a low of 21.5 exchanges in CAST/Ei to a high of 24.9 in SPRET/Ei. We also found that, as expected, these crossover events were nonrandomly distributed and displayed positive interference. However, we found no evidence for significant differences in the patterns of crossover positioning between strains with different exchange frequencies. From our observations of >10,000 autosomal synaptonemal complexes, we conclude that achiasmate bivalents arise in the male mouse at a frequency of 0.1%. Thus, special mechanisms that segregate achiasmate chromosomes are unlikely to be an important component of mammalian male meiosis.

scholarly journals EVIDENCE THAT TWO LOCI PREDOMINANTLY DETERMINE THE DIFFERENCE IN SUSCEPTIBILITY TO THE HIGH PRESSURE NEUROLOGIC SYNDROME TYPE I SEIZURE IN MICE

Genetics ◽  
1981 ◽  
Vol 99 (2) ◽  
pp. 285-307
Author(s):  
R D McCall ◽  
D Frierson
Keyword(s):  
High Pressure ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Chromosome 17 ◽  
Seizure Threshold ◽  
Mouse Strains ◽  
Compression Rate ◽  
Type I ◽  
Major Locus ◽  
The Difference

ABSTRACT Most mammals tested, when exposed to increasing pressure in helium/oxygen atmospheres, exhibit progressive motor disturbances culminating in two, usually successive, well-differentiated convulsive seizures. The seizures are highly reproducible components of the constellation of events that collectively constitute the High Pressure Neurologic Syndrome (HPNS). In the present study, we present evidence that the mean difference in seizure threshold pressures of the first seizure to occur (HPNS Type I) between inbred mouse strains DBA/2J and C57BL/6J is predominantly determined (> 60%) by the expression of a major locus—possibly linked to the H-2 locus on chromosome 17—and a minor locus, probably unlinked. This outcome is derived from applications of the maximum likelihood modeling procedure of Elston and Stewart (1973) and Stewart and Elston (1973) to eleven models of genetic determinacy and tests (including breeding tests) of "preferred" models so derived using BXD recombinant inbred strains that show the following: The major locus exhibits conditional dominance characteristics depending upon compression rate and minor locus genotype. At a constant mean compression rate of 100 atm hr-1, the major locus manifests strong, though incomplete, dominance apparently independent of minor locus genotype. Its expression is, however, highly sensitive to compression rate, losing its dominance altogether at a linear rate of 1,000 atm hr-1. The major locus interacts with the weakly dominant and relatively compression-rate-insensitive minor locus to retain dominance at fast compression only when the dominant alleles of both loci are present. A principal finding of this study is that employing two compression rates permits fuller genetic characterization of murine high-pressure seizure susceptibility differences than could be achieved by use of a single compression rate.

scholarly journals THE Ah PHENOTYPE. SURVEY OF FORTY-EIGHT RAT STRAINS AND TWENTY INBRED MOUSE STRAINS

Genetics ◽  
1982 ◽  
Vol 100 (1) ◽  
pp. 79-87
Author(s):  
Daniel W Nebert ◽  
Nancy M Jensen ◽  
Hisashi Shinozuka ◽  
Heinz W Kunz ◽  
Thomas J Gill
Keyword(s):  
Specific Activity ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Mouse Strains ◽  
Ah Receptor ◽  
Inbred Mouse Strains ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Specific Activities ◽  
Inbred Rat

ABSTRACT Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.

scholarly journals Dysregulated expression of the T cell cytokine Eta-1 in CD4-8- lymphocytes during the development of murine autoimmune disease.

1990 ◽  
Vol 172 (4) ◽  
pp. 1177-1183 ◽  
Author(s):  
R Patarca ◽  
F Y Wei ◽  
P Singh ◽  
M I Morasso ◽  
H Cantor
Keyword(s):  
T Cell ◽  
B Cells ◽  
Autoimmune Disease ◽  
Cell Activation ◽  
Cell Clone ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Mouse Strains ◽  
Effector Cells ◽  
T Cell Clone

The development of autoimmune disease in the MRL/MpJ-lpr inbred mouse strain depends upon the maturation of a subset of T lymphocytes that may cause sustained activation of immunological effector cells such as B cells and macrophages. We tested the hypothesis that abnormal effector cell activation reflects constitutive overexpression of a T cell cytokine. We found that a newly defined T cell cytokine, Eta-1, is expressed at very high levels in T cells from MRL/l mice but not normal mouse strains and in a CD4-8- 45R+ T cell clone. The Eta-1 gene encodes a secreted protein that binds specifically to macrophages, possibly via a cell adhesion receptor, resulting in alterations in the mobility and activation state of this cell type (Patarca, R., G. J. Freeman, R. P. Singh, et al. 1989. J. Exp. Med. 170:145; Singh, R. P., R. Patarca, J. Schwartz, P. Singh, and H. Cantor. 1990. J. Exp. Med. 171:1931). In addition, recent studies have indicated that Eta-1 can enhance secretion of IgM and IgG by mixtures of macrophages and B cells (Patarca, R., M. A. Lampe, M. V. Iregai, and H. Cantor, manuscript in preparation). Dysregulation of Eta-1 expression begins at the onset of autoimmune disease and continues throughout the course of this disorder. Maximal levels of Eta-1 expression and the development of severe autoimmune disease reflect the combined contribution of the lpr gene and MRL background genes.

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