Immunity toTrichuris murisin the laboratory mouse

2003 ◽  
Vol 77 (2) ◽  
pp. 95-98 ◽  
Author(s):  
K.J. Else ◽  
M.L. deSchoolmeester
Keyword(s):  
Laboratory Mouse ◽  
Mouse Strains ◽  
Chronic Infections ◽  
Trichuris Muris ◽  
Intestinal Nematode ◽  
Unique Model ◽  
Resistance To Infection ◽  
Laboratory Models ◽  
Strain Dependent

AbstractOf all the laboratory models of intestinal nematode infection,Trichuris murisin the mouse is arguably the most powerful. This is largely due to the fact that the ability to expel this parasite is strain dependent. Thus, most mouse strains readily expelT. muris. However certain mouse strains, and indeed some individuals within particular mouse strains, are unable to mount a protective immune response and harbour long term chronic infections. This unique model thus presents an opportunity to examine the immune events underlying both resistance to infection and persistent infection within the same host species, and in some cases, the same host strain.

Differential Maintenance and Frequency-Dependent Tuning of LTP at Hippocampal Synapses of Specific Strains of Inbred Mice

2000 ◽  
Vol 84 (5) ◽  
pp. 2484-2493 ◽  
Author(s):  
Peter V. Nguyen ◽  
Steven N. Duffy ◽  
Jennie Z. Young
Keyword(s):  
Genetic Background ◽  
Pyramidal Neurons ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Synaptic Facilitation ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Synapses ◽  
Strain Dependent

Transgenic and knockout mice are used extensively to elucidate the molecular mechanisms of hippocampal synaptic plasticity. However, genetic and phenotypic variations between inbred mouse strains that are used to construct genetic models may confound the interpretation of cellular neurophysiological data derived from these models. Using in vitro slice stimulation and recording methods, we compared the membrane biophysical, cellular electrophysiological, and synaptoplastic properties of hippocampal CA1 neurons in four specific strains of inbred mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms/J. Hippocampal long-term potentiation (LTP) induced by theta-pattern stimulation, and by repeated multi-burst 100-Hz stimulation at various interburst intervals, was better maintained in area CA1 of slices from BL/6J mice than in slices from CBA and DBA mice. At an interburst interval of 20 s, maintenance of LTP was impaired in CBA and DBA slices, as compared with BL/6J slices. When the interburst interval was reduced to 3 s, induction of LTP was significantly enhanced in129/SvEms slices, but not in DBA and CBA slices. Long-term depression (LTD) was not significantly different between slices from these four strains. For the four strains examined, CA1 pyramidal neurons showed no significant differences in spike-frequency accommodation, membrane input resistance, and number of spikes elicited by current injection. Synaptically-evoked glutamatergic postsynaptic currents did not significantly differ among CA1 pyramidal neurons in these four strains. Since the observed LTP deficits resembled those previously seen in transgenic mice with reduced hippocampal cAMP-dependent protein kinase (PKA) activity, we searched for possible strain-dependent differences in cAMP-dependent synaptic facilitation induced by forskolin (an activator of adenylate cyclase) and IBMX (a phosphodiesterase inhibitor). We found that forskolin/IBMX-induced synaptic facilitation was deficient in area CA1 of DBA/2J and CBA/J slices, but not in BL/6J and 129/SvEms/J slices. These defects in cAMP-induced synaptic facilitation may underlie the deficits in memory, observed in CBA/J and DBA/2J mice, that have been previously reported. We conclude that hippocampal LTP is influenced by genetic background and by the temporal characteristics of the stimulation protocol. The plasticity of hippocampal synapses in some inbred mouse strains may be “tuned” to particular temporal patterns of synaptic activity. From a broader perspective, our data support the notion that strain-dependent variation in genetic background is an important factor that can influence the synaptoplastic phenotypes observed in studies that use genetically modified mice to explore the molecular bases of synaptic plasticity.

scholarly journals On the Use of Heterogeneous Stock Mice to Map Transcriptomes Associated With Excessive Ethanol Consumption

2021 ◽  
Vol 12 ◽  
Author(s):  
Robert Hitzemann ◽  
Denesa R. Lockwood ◽  
Angela R. Ozburn ◽  
Tamara J. Phillips
Keyword(s):  
Gene Networks ◽  
Inbred Mouse ◽  
Laboratory Mouse ◽  
Ethanol Consumption ◽  
Mouse Strains ◽  
Ethanol Preference ◽  
Background Data ◽  
And Behavior ◽  
Binge Ethanol

We and many others have noted the advantages of using heterogeneous (HS) animals to map genes and gene networks associated with both behavioral and non-behavioral phenotypes. Importantly, genetically complex Mus musculus crosses provide substantially increased resolution to examine old and new relationships between gene expression and behavior. Here we report on data obtained from two HS populations: the HS/NPT derived from eight inbred laboratory mouse strains and the HS-CC derived from the eight collaborative cross inbred mouse strains that includes three wild-derived strains. Our work has focused on the genes and gene networks associated with risk for excessive ethanol consumption, individual variation in ethanol consumption and the consequences, including escalation, of long-term ethanol consumption. Background data on the development of HS mice is provided, including advantages for the detection of expression quantitative trait loci. Examples are also provided of using HS animals to probe the genes associated with ethanol preference and binge ethanol consumption.

scholarly journals Muc5ac: a critical component mediating the rejection of enteric nematodes

2011 ◽  
Vol 208 (5) ◽  
pp. 893-900 ◽  
Author(s):  
Sumaira Z. Hasnain ◽  
Christopher M. Evans ◽  
Michelle Roy ◽  
Amanda L. Gallagher ◽  
Kristen N. Kindrachuk ◽  
...  
Keyword(s):  
De Novo ◽  
Trichinella Spiralis ◽  
Nematode Infection ◽  
Nippostrongylus Brasiliensis ◽  
Chronic Infections ◽  
Trichuris Muris ◽  
Intestinal Nematode ◽  
Ifn Γ ◽  
Deficient Mice

De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong TH2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the TH1 cytokine IFN-γ. Because TH1 inflammation is thought to favor chronic nematode infection, IFN-γ was neutralized in vivo, resulting in an even stronger TH2-type immune response. Nevertheless, despite a more robust TH2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection.

scholarly journals Evidence for Genetic Modifiers of Ovarian Follicular Endowment and Development from Studies of Five Inbred Mouse Strains

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Jacqueline Canning ◽  
Yasushi Takai ◽  
Jonathan L. Tilly
Keyword(s):  
Genetic Manipulation ◽  
Inbred Mouse ◽  
Laboratory Mouse ◽  
Growth Patterns ◽  
Mouse Strains ◽  
Genetic Modifiers ◽  
Follicle Growth ◽  
Primary Follicle ◽  
Primordial Follicles ◽  
Strain Dependent

Abstract The laboratory mouse is the model of choice for genetic studies in mammals due to the availability of many genetically defined inbred strains and inbred congenic strains, as well as the ability to study the effects of over-expression (transgenics) or inactivation (knockouts) of a given gene on cells or tissues. During our studies using these technologies to uncover the importance of various genes to apoptosis in the ovary, we observed that the size of the primordial oocyte reserve was affected by mouse strain in the absence of any other genetic manipulation. To determine if genetic modifiers of oocyte endowment truly exist, herein we examined follicle numbers in one outbred (CD-1) and several inbred (129/Sv, DBA/2, C57BL/6, FVB, AKR/J) strains of mice at day 4 (neonatal) and day 42 (young adult) postpartum. In neonatal life, ovaries of AKR/J females had the lowest total number of follicles, whereas 129/Sv females possessed the highest total number of follicles (P < 0.05 for AKR/J versus 129/Sv). There were more primordial follicles in 129/Sv compared with DBA/2 (P < 0.05), C57BL/6 (P < 0.05), FVB (P < 0.05) or AKR/J (P < 0.05) females, and in CD-1 compared with AKR/J (P < 0.05) females. Although no significant strain-dependent differences in primary follicle numbers were noted, C57BL/6 females had the fewest number of small preantral follicles (P < 0.05 versus all other strains). Evaluation of ovaries at 42 days of age revealed the persistence of strain-dependent differences in early follicle growth patterns, although the total numbers of follicles were comparable. Of interest, marked strain-dependent differences in the rate of primordial follicle growth activation, as well as in the rate of follicle loss (atresia), between days 4 and 42 were observed. These results indicate that genetic modifiers play a major role in follicle endowment, development and atresia in the mouse ovary.

scholarly journals Evaluation of Moxifloxacin-Containing Regimens in Pathologically Distinct Murine Tuberculosis Models

2015 ◽  
Vol 59 (7) ◽  
pp. 4026-4030 ◽  
Author(s):  
Si-Yang Li ◽  
Scott M. Irwin ◽  
Paul J. Converse ◽  
Khisi E. Mdluli ◽  
Anne J. Lenaerts ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Predictive Accuracy ◽  
Term Treatment ◽  
Mouse Strains ◽  
Disappointing Result ◽  
Similar Treatment ◽  
Infection Models ◽  
Long Term Treatment ◽  
Aerosol Infection

ABSTRACTIn the recently concluded REMox-TB trial, two 4-month moxifloxacin-containing regimens did not meet the criteria for noninferiority compared to the current 6-month first-line regimen to treat tuberculosis (TB). Despite the disappointing result, this phase 3 clinical trial provides a rare opportunity to gauge the predictive accuracy of the nonclinical models used to support regimen development. In parallel with the REMox-TB trial, we compared the efficacy of the same three regimens against chronic TB infection in the commonly used BALB/c mouse strain and in C3HeB/FeJ mice, which have attracted recent interest as a nonclinical efficacy model because they develop caseous lung lesions which may better resemble human TB. In long-term treatment experiments at two institutions, using low-dose aerosol infection models with 6- to 8-week incubation periods in both mouse strains, control mice received rifampin, isoniazid, pyrazinamide, and ethambutol (RHZE), and test mice received the same regimen with moxifloxacin replacing isoniazid (RMZE) or ethambutol (RHZM). Outcome measures were lung CFU counts during treatment and relapse after various durations of treatment. At both institutions and in both mouse strains, RMZE and RHZM reduced by approximately 1 month and 0 to 1 month, respectively, the treatment duration needed to produce the same relapse rate as RHZE. These results demonstrating generally similar treatment-shortening effects of the moxifloxacin-containing regimens in each mouse strain, with effect sizes consistent with the REMox-TB trial results, reinforce the predictive value of murine models for TB regimen development.

Quantitating Aortic Atherosclerosis in Rabbits and Mice

1997 ◽  
Vol 3 (S2) ◽  
pp. 317-318
Author(s):  
David A. Sanan ◽  
Dale L. Newland
Keyword(s):  
Gene Knockout ◽  
Laboratory Mouse ◽  
Lipoprotein Metabolism ◽  
Wild Type Mouse ◽  
Mouse Strains ◽  
Chow Diet ◽  
Homologous Genes ◽  
Normal Chow ◽  
Metabolism Gene ◽  
Knockout Technology

Build-up of visible atherosclerotic plaque in the arteries is readily quantifiable. The mouse and the rabbit provide useful models for understanding the pathogenesis of atherosclerosis by investigating the effects of genetic and dietary perturbations.Although the wild type mouse does not develop atherosclerosis, atherosclerosis susceptibility genes have been identified in some laboratory mouse strains which do. Furthermore, transgenic technology and gene targeting have produced genetically modified mice that express various apolipoproteins, enzymes and cofactors involved in human lipoprotein metabolism. Gene “knockout” technology allows transgene expression without interference from homologous genes. One notable “knockout” mouse, deficient in apolipoprotein E, develops spontaneous atherosclerosis on a normal chow diet. Transgenic modulations of the atherosclerotic responses of these highly susceptible mice are more pronounced and easily measured. Small, cheap and fast breeding, mice are convenient animal models. But to make mice susceptible to atherosclerosis, their genetic background has to be so drastically altered that the resulting lipoprotein metabolism may not model the human metabolism accurately enough.

scholarly journals Influence of the Bcg Locus on Natural Resistance to Primary Infection with the Facultative Intracellular Bacterium Francisella tularensis in Mice

2000 ◽  
Vol 68 (3) ◽  
pp. 1480-1484 ◽  
Author(s):  
Hana Kovářová ◽  
Lenka Hernychová ◽  
Marián Hajdúch ◽  
M. Šírová ◽  
Aleš Macela
Keyword(s):  
Francisella Tularensis ◽  
Bacterial Colonization ◽  
Phenotypic Expression ◽  
Interleukin 10 ◽  
Natural Resistance ◽  
Mouse Strains ◽  
Oxygen Intermediates ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Resistance To Infection

ABSTRACT The implication of the Bcg locus in the control of natural resistance to infection with a live vaccine strain (LVS) of the intracellular pathogen Francisella tularensis was studied. Analysis of phenotypic expression of natural resistance and susceptibility was performed using mouse strains congenic at theBcg locus. Comparison of the kinetics of bacterial colonization of spleen showed that B10.A.Bcg(r) mice were extremely susceptible during early phases of primary sublethal infection, while their congenic C57BL/10N [Bcg(s)] counterparts could be classified as resistant to F. tularensis LVS infection according to the 2-log-lower bacterial CFU within the tissue as long as 5 days after infection. Different phenotypes of Bcg congenic mice were associated with differential expression of the cytokines tumor necrosis factor alpha, interleukin-10, and gamma interferon and production of reactive oxygen intermediates. These results strongly suggest that the Bcglocus, which is close or identical to the Nramp1 gene, controls natural resistance to infection by F. tularensisand that its effect is the opposite of that observed for otherBcg-controlled pathogens.

Selection of sheep for response to Trichostrongylus colubriformis larvae: genetic parameters

2001 ◽  
Vol 73 (1) ◽  
pp. 41-48 ◽  
Author(s):  
R. R. Woolastont ◽  
R. G. Windon
Keyword(s):  
Genetic Correlation ◽  
Secondary Infection ◽  
Selection Criterion ◽  
Breeding Programme ◽  
Secondary Field ◽  
Trichostrongylus Colubriformis ◽  
Phenotypic Correlations ◽  
Intestinal Nematode ◽  
The Mean

AbstractData were analysed from a long-term selection experiment with Merino sheep, based on immunological responsiveness to the intestinal nematode Trichostrongylus colubriformis. For the first 14 years of selection, the criterion was the mean of five fortnightly faecal worm-egg counts (FECs) of pen-housed lambs that were vaccinated with irradiated larvae then challenged with normal T. colubriformis larvae. For most of the lambs born in the subsequent 6 years, the selection criterion was the mean of three weekly FECs of grazing lambs following a secondary challenge with T. colubriformis larvae. Data from 2233 lambs were included in the analyses.At the end of the experiment, the lines selected for high and low response to challenge differed by 2·3 to 2·9 phenotypic standard deviations. The heritability of average pen-tested FEC was 0·38 (s.e. 0·04), similar to that for average FEC after secondary field challenge (0·37, s.e. 007). Average FECs from the primary field challenge were less heritable (0·21, s.e. 006). Counts recorded on pen-tested animals at 3, 5, 7, 9 and 11 weeks after infection were all highly correlated genetically (estimates 0·93 to 0·99) and of similar heritability (0·33 to 0·39) with a non-significant tendency for later FECs to be more heritable. Phenotypic correlations were lower, ranging from 0·60 for counts 8 weeks apart, to 0·78 to 0·81 for adjacent samples 2 weeks apart. Single-record heritability estimates at 3, 4 and 5 weeks after secondary infection in grazing lambs did not differ statistically from each other but were highest at the 5th week after infection at 0·33 (s.e. 007).FECs determined in pens were imperfectly correlated with FECs determined at pasture (genetic correlation 0·72, s.e. 013). Phenotypic correlations of single-record FECs across primary and secondary field challenges were low (around 0·2), although the genetic correlation between mean primary FEC and mean secondary FEC was not significantly different from unity. Testing under standardized conditions in pens did not result in consistently higher heritabilities than testing immunologically primed lambs at pasture. Repeated measurement in a breeding programme offers little additional benefit, except when lambs have had ample prior experience of parasite infection, with the two measures separated by an anthelmintic treatment. If an objective of a Merino breeding programme is to reduce FEC under field conditions, then using one measure in the field, approximately 3 to 5 weeks after a secondary artificial infection, is likely to lead to long-term progress.

scholarly journals MoG+: a database of genomic variations across three mouse subspecies for biomedical research

2021 ◽  
Author(s):  
Toyoyuki Takada ◽  
Kentaro Fukuta ◽  
Daiki Usuda ◽  
Tatsuya Kushida ◽  
Shinji Kondo ◽  
...  
Keyword(s):  
Phenotypic Diversity ◽  
Laboratory Mouse ◽  
Genomic Analysis ◽  
Inbred Strains ◽  
Genetic Distances ◽  
Mouse Strains ◽  
Comparative Genomic ◽  
Genome Database ◽  
Data Resource ◽  
Genomic Variations

AbstractLaboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.

scholarly journals Transketolase is involved in the control of Sigma B during chronic infection by Staphylococcus aureus

2019 ◽  
Author(s):  
Xin Tan ◽  
Elodie Ramond ◽  
Anne Jamet ◽  
Baptiste Decaux-Tramoni ◽  
Marion Dupuis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wild Type Strain ◽  
Pentose Phosphate ◽  
Chronic Infections ◽  
Master Regulators ◽  
Sigma B ◽  
Viable Bacteria ◽  
Infected Cells ◽  
Slow Growing

AbstractStaphylococcus aureus is a leading cause of both acute and chronic infections in humans. Its ability to persist within host cells is thought to play an important role in chronicity and treatment failures. The importance of the pentose phosphate pathway (PPP) during S. aureus chronic infection is currently largely unexplored. Here, we focused on one key PPP enzyme, transketolase. We showed that inactivation of the unique gene encoding transketolase activity in S. aureus USA300 (Δtkt) led to an impaired growth in broth. Using time-lapse video imaging, we correlated this phenotype with a defect in early intracellular proliferation compared to wild-type strain. As determined by metabolomic analysis, tkt inactivation also had an important impact on S. aureus metabolism. We then monitored long-term intracellular persistence over 10 days by counting of viable bacteria. Unexpectedly for such a slow-growing strain, the Δtkt mutant was almost completely eliminated by endothelial cells after ten days, as opposed to a prototypical slow-growing ΔhemDBL mutant for which we recovered 1,000 fold more viable bacteria. We found that in infected cells, the transcriptional activity of the two master regulators Sigma B and RpiRc was drastically reduced in the Δtkt mutant compared to wild-type strain. Concomitantly, RNAIII transcription was strongly increased. This transcriptional profile is likely to explain the inability of this slow-growing mutant to sustain long-term intracellular survival, suggesting that TKT -or a functional PPP-is required for intracellular bacteria to enable a transcriptional program geared towards persistence.ImportanceStaphylococcus aureus is a leading cause of severe bacterial infections. This bacterium is readily internalized by non-professional phagocytes and infected cells have been proposed to play an important role in chronic infections and treatment failures.Here, we show the importance of the unique transketolase TKT of S. aureus USA300 in bacterial adaptation during chronic intracellular infection. We show that TKT is mandatory for the metabolomic homeostasis of S. aureus during intracellular persistence. This work unravels the critical role of TKT in the transcriptional regulation of the master regulators Sigma B, RpiRc and RNAIII linking the pentose phosphate pathway to the control of chronic S. aureus infections.

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