scholarly journals Genetic Analysis of Bphse: a Novel Gene Complementing Resistance to Bordetella pertussis-Induced Histamine Sensitization

2021 ◽  
Author(s):  
Cory Teuscher ◽  
Abbas Raza ◽  
Sean A Diehl ◽  
Laure K Case ◽  
Dimitry N Krementsov ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Histamine Receptor ◽  
Mouse Strains ◽  
Modifier Locus ◽  
Association Testing ◽  
Multiple Loci ◽  
Genetic And Environmental Factors

Histamine is a bioactive amine associated with a plethora of normal and pathophysiological processes, with the latter being dependent on both genetic and environmental factors including infectious agents. Previously, we showed in mice that susceptibility to Bordetella pertussis and pertussis toxin (PTX) induced histamine sensitization (Bphs) is controlled by histamine receptor H1 (Hrh1/HRH1) alleles. Bphs susceptible and resistant alleles (Bphss/Bphsr) encode for two-conserved protein haplotypes. Given the importance of HRH1 signaling in health and disease, we sequenced Hrh1 across an extended panel of laboratory and wild-derived inbred strains and phenotyped them for Bphs. Unexpectedly, eight strains homozygous for the Bphsr allele phenotyped as Bphss, suggesting the existence of a modifying locus segregating among the strains capable of complementing Bphsr. Genetic analyses mapped this modifier locus to mouse chromosome 6; designated Bphs-enhancer (Bphse), within a functional linkage disequilibrium domain encoding multiple loci controlling responsiveness to histamine (Bphs/Hrh1 and Histh1-4). Interval-specific single-nucleotide polymorphism (SNP) based association testing across 50 laboratory and wild-derived inbred mouse strains and functional prioritization analyses resulted in the identification of candidate genes for Bphse within a ~5.5 Mb interval (Chr6:111.0-116.4 Mb), including Atg7, Plxnd1, Tmcc1, Mkrn2, Il17re, Pparg, Lhfpl4, Vgll4, Rho and Syn2. Taken together, these results demonstrate the power of combining network-based computational methods with the evolutionarily significant diversity of wild-derived inbred mice to identify novel genetic mechanisms controlling susceptibility and resistance to histamine shock.

scholarly journals The genetic architecture of NAFLD among inbred strains of mice

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Simon T Hui ◽  
Brian W Parks ◽  
Elin Org ◽  
Frode Norheim ◽  
Nam Che ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Association Studies ◽  
Inbred Mouse ◽  
Liver Steatosis ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Genome Wide Association Studies ◽  
Alcoholic Fatty Liver ◽  
Genetic And Environmental Factors

To identify genetic and environmental factors contributing to the pathogenesis of non-alcoholic fatty liver disease, we examined liver steatosis and related clinical and molecular traits in more than 100 unique inbred mouse strains, which were fed a diet rich in fat and carbohydrates. A >30-fold variation in hepatic TG accumulation was observed among the strains. Genome-wide association studies revealed three loci associated with hepatic TG accumulation. Utilizing transcriptomic data from the liver and adipose tissue, we identified several high-confidence candidate genes for hepatic steatosis, including Gde1, a glycerophosphodiester phosphodiesterase not previously implicated in triglyceride metabolism. We confirmed the role of Gde1 by in vivo hepatic over-expression and shRNA knockdown studies. We hypothesize that Gde1 expression increases TG production by contributing to the production of glycerol-3-phosphate. Our multi-level data, including transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis.

Genetic Analysis of Crown Size in the First Molars Using SMXA Recombinant Inbred Mouse Strains

2004 ◽  
Vol 83 (1) ◽  
pp. 45-49 ◽  
Author(s):  
T. Shimizu ◽  
H. Oikawa ◽  
J. Han ◽  
E. Kurose ◽  
T. Maeda
Keyword(s):  
Recombinant Inbred ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Tooth Crown ◽  
Mean Values ◽  
Genome Wide ◽  
Inbred Strains Of Mice ◽  
Genetic And Environmental Factors ◽  
Crown Size

Tooth crown size may be determined by both genetic and environmental factors. The aim of this study was to identify quantitative trait loci (QTLs) affecting dental crown size and determine whether there is genetic independence between upper and lower teeth, using SMXA recombinant inbred strains of mice. Mesiodistal and buccolingual crown diameters (MD and BL, respectively) of the upper and lower first molars (M1 and M1, respectively) were measured. For each trait, mean values of substrains showed a continuous spectrum of distribution. Genome-wide scan detected QTLs exceeding suggestive threshold levels for MD of M1 (chromosomes 7, 13, and 17), BL of M1 (chromosomes 8 and 13), MD of M1 (chromosomes 7 and 13), and BL of M1 (chromosomes 3 and 15). These findings suggest that tooth crown size is controlled by multiple genes, and that there is some independence of genetic control between M1 and M1.

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 Terc Gene Cluster Variants Predict Liver Telomere Length in Mice

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2623
Author(s):  
Dana Zeid ◽  
Sean Mooney-Leber ◽  
Laurel R. Seemiller ◽  
Lisa R. Goldberg ◽  
Thomas J. Gould
Keyword(s):  
Linkage Disequilibrium ◽  
Telomere Length ◽  
Gene Cluster ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Chromosome 3 ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Initial Finding

Variants in a gene cluster upstream-adjacent to TERC on human chromosome 3, which includes genes APRM, LRRC31, LRRC34 and MYNN, have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the TERC gene cluster influence telomere length in humans is unknown. Given the proximity between the TERC gene cluster and TERC (~0.05 Mb) in humans, it is speculated that cluster variants are in linkage disequilibrium with a TERC causal variant. In mice, the Terc gene/Terc gene cluster are also located on chromosome 3; however, the Terc gene cluster is located distantly downstream of Terc (~60 Mb). Here, we initially aim to investigate the interactions between genotype and nicotine exposure on absolute liver telomere length (aTL) in a panel of eight inbred mouse strains. Although we found no significant impact of nicotine on liver aTL, this first experiment identified candidate single nucleotide polymorphisms (SNPs) in the murine Terc gene cluster (within genes Lrrc31, Lrriq4 and Mynn) co-varying with aTL in our panel. In a second experiment, we tested the association of these Terc gene cluster variants with liver aTL in an independent panel of eight inbred mice selected based on candidate SNP genotype. This supported our initial finding that Terc gene cluster polymorphisms impact aTL in mice, consistent with data in human populations. This provides support for mice as a model for telomere dynamics, especially for studying mechanisms underlying the association between Terc cluster variants and telomere length. Finally, these data suggest that mechanisms independent of linkage disequilibrium between the Terc/TERC gene cluster and the Terc/TERC gene mediate the cluster’s regulation of telomere length.

scholarly journals Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains

2010 ◽  
Vol 42A (2) ◽  
pp. 103-113 ◽  
Author(s):  
Matthew S. Barnabei ◽  
Nathan J. Palpant ◽  
Joseph M. Metzger
Keyword(s):  
Cardiac Function ◽  
Genetic Divergence ◽  
Ex Vivo ◽  
Inbred Mouse ◽  
Critical Role ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Cardiac Decompensation

Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.

scholarly journals Mouse Susceptibility to Anthrax Lethal Toxin Is Influenced by Genetic Factors in Addition to Those Controlling Macrophage Sensitivity

2004 ◽  
Vol 72 (8) ◽  
pp. 4439-4447 ◽  
Author(s):  
Mahtab Moayeri ◽  
Nathaniel W. Martinez ◽  
Jason Wiggins ◽  
Howard A. Young ◽  
Stephen H. Leppla
Keyword(s):  
Genetic Factors ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Lethal Toxin ◽  
Cytokine Response ◽  
Mouse Strains ◽  
Anthrax Lethal Toxin ◽  
Toll Like Receptor 4 ◽  
Oxide Synthase

ABSTRACT Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (Mφ) derived from certain inbred strains. We used nine inbred strains and two inducible nitric oxide synthase (iNOS) knockout C57BL/6J strains polymorphic for the LT Mφ sensitivity Kif1C locus to analyze the role of Mφ sensitivity (to lysis) in LT-mediated cytokine responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, eotaxin, and interleukin-1β occurred only in mice having LT-sensitive Mφ. However, while iNOS knockout C57BL/6J mice having LT-sensitive Mφ were much more susceptible to LT than the knockout mice with LT-resistant Mφ, a comparison of susceptibilities to LT in the larger set of inbred mouse strains showed a lack of correlation between Mφ sensitivity and animal susceptibility to toxin. For example, C3H/HeJ mice, harboring LT-sensitive Mφ and having the associated LT-mediated cytokine response, were more resistant than mice with LT-resistant Mφ and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also found that CAST/Ei mice are uniquely sensitive to LT and may provide an economical bioassay for toxin-directed therapeutics. The data indicate that while the cytokine response to LT in mice requires Mφ lysis and while Mφ sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality of that strain, the contribution of Mφ sensitivity and cytokine response to animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated lethality in mice is influenced by genetic factors in addition to those controlling Mφ lysis and cytokine response and is independent of Tlr4 function.

scholarly journals Large-scale, high-throughput screening for coagulation and hematologic phenotypes in mice*

2002 ◽  
Vol 11 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Luanne L. Peters ◽  
Eleanor M. Cheever ◽  
Heather R. Ellis ◽  
Phyllis A. Magnani ◽  
Karen L. Svenson ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Sample Volume ◽  
Small Sample ◽  
Mouse Strains ◽  
Phenotypic Data ◽  
Multiple Tests

The Mouse Phenome Project is an international effort to systematically gather phenotypic data for a defined set of inbred mouse strains. For such large-scale projects the development of high-throughput screening protocols that allow multiple tests to be performed on a single mouse is essential. Here we report hematologic and coagulation data for more than 30 inbred strains. Complete blood counts were performed using an Advia 120 analyzer. For coagulation testing, we successfully adapted the Dade Behring BCS automated coagulation analyzer for use in mice by lowering sample and reagent volume requirements. Seven automated assay procedures were developed. Small sample volume requirements make it possible to perform multiple tests on a single animal without euthanasia, while reductions in reagent volume requirements reduce costs. The data show that considerable variation in many basic hematological and coagulation parameters exists among the inbred strains. These data, freely available on the World Wide Web, allow investigators to knowledgeably select the most appropriate strain(s) to meet their individual study designs and goals.

scholarly journals Role of Genetic Resistance in Invasive Pneumococcal Infection: Identification and Study of Susceptibility and Resistance in Inbred Mouse Strains

2001 ◽  
Vol 69 (1) ◽  
pp. 426-434 ◽  
Author(s):  
Neill A. Gingles ◽  
Janet E. Alexander ◽  
Aras Kadioglu ◽  
Peter W. Andrew ◽  
Alison Kerr ◽  
...  
Keyword(s):  
Inbred Mice ◽  
Inbred Mouse ◽  
Genetic Resistance ◽  
Pneumococcal Infection ◽  
Mouse Strains ◽  
Inflammatory Lesions ◽  
Invasive Pneumococcal Infection ◽  
Susceptibility And Resistance

ABSTRACT From a panel of nine inbred mice strains intranasally infected withStreptococcus pneumoniae type 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial clearance. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca but not BALB/c mice. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 h postinfection. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice, and there was a greater cellular infiltration into the lung tissue of BALB/c mice at the earlier time points. Our data suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils.

scholarly journals Hydronephrosis in inbred strains of mice with particular reference to the BRVR strain

1973 ◽  
Vol 7 (3) ◽  
pp. 229-236 ◽  
Author(s):  
D. M. Taylor ◽  
H. Fraser
Keyword(s):  
Inbred Mouse ◽  
Inbred Strains ◽  
The Other ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Concomitant Infection ◽  
Inbred Strains Of Mice ◽  
Dietary Variation

Hydronephrosis occurred in 6 of the 13 inbred mouse strains maintained in the same colony. Its incidence was high only in the BRVR strain, where about half of the cases could only be detected microscopically. There was no concomitant infection even in severely abnormal BRVR kidneys and the incidence of the condition was not influenced by dietary variation. The hydronephrosis found, less frequently, in 5 of the other strains was of a different type from that in BRVR mice.

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