scholarly journals What Have We Learned (or Expect to) From Analysis of Murine Genetic Models Related to Substance Use Disorders?

2022 ◽  
Vol 12 ◽  
Author(s):  
Gary Peltz ◽  
Yalun Tan
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Genetic Factors ◽  
Drugs Of Abuse ◽  
Inbred Mouse ◽  
Public Health Problem ◽  
Mouse Genetics ◽  
Genetic Models ◽  
Mouse Strains ◽  
Insight Into

The tremendous public health problem created by substance use disorders (SUDs) presents a major opportunity for mouse genetics. Inbred mouse strains exhibit substantial and heritable differences in their responses to drugs of abuse (DOA) and in many of the behaviors associated with susceptibility to SUD. Therefore, genetic discoveries emerging from analysis of murine genetic models can provide critically needed insight into the neurobiological effects of DOA, and they can reveal how genetic factors affect susceptibility drug addiction. There are already indications, emerging from our prior analyses of murine genetic models of responses related to SUDs that mouse genetic models of SUD can provide actionable information, which can lead to new approaches for alleviating SUDs. Lastly, we consider the features of murine genetic models that enable causative genetic factors to be successfully identified; and the methodologies that facilitate genetic discovery.

scholarly journals Interactions of neuroimmune signaling and glutamate plasticity in addiction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Cassandra D. Gipson ◽  
Scott Rawls ◽  
Michael D. Scofield ◽  
Benjamin M. Siemsen ◽  
Emma O. Bondy ◽  
...  
Keyword(s):  
Substance Use ◽  
Drug Use ◽  
Substance Use Disorders ◽  
Drugs Of Abuse ◽  
Treatment Strategies ◽  
Glutamate Signaling ◽  
Open Questions ◽  
Seeking Behavior ◽  
Glutamate System ◽  
Chronic Use

AbstractChronic use of drugs of abuse affects neuroimmune signaling; however, there are still many open questions regarding the interactions between neuroimmune mechanisms and substance use disorders (SUDs). Further, chronic use of drugs of abuse can induce glutamatergic changes in the brain, but the relationship between the glutamate system and neuroimmune signaling in addiction is not well understood. Therefore, the purpose of this review is to bring into focus the role of neuroimmune signaling and its interactions with the glutamate system following chronic drug use, and how this may guide pharmacotherapeutic treatment strategies for SUDs. In this review, we first describe neuroimmune mechanisms that may be linked to aberrant glutamate signaling in addiction. We focus specifically on the nuclear factor-kappa B (NF-κB) pathway, a potentially important neuroimmune mechanism that may be a key player in driving drug-seeking behavior. We highlight the importance of astroglial-microglial crosstalk, and how this interacts with known glutamatergic dysregulations in addiction. Then, we describe the importance of studying non-neuronal cells with unprecedented precision because understanding structure-function relationships in these cells is critical in understanding their role in addiction neurobiology. Here we propose a working model of neuroimmune-glutamate interactions that underlie drug use motivation, which we argue may aid strategies for small molecule drug development to treat substance use disorders. Together, the synthesis of this review shows that interactions between glutamate and neuroimmune signaling may play an important and understudied role in addiction processes and may be critical in developing more efficacious pharmacotherapies to treat SUDs.

Manipulation of the immune response in parasitic infections

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 665-675
Author(s):  
J.G. Howard
Keyword(s):  
Immune Response ◽  
Inbred Mouse ◽  
Lymphocyte Subset ◽  
Mouse Strains ◽  
Parasitic Infections ◽  
Research Experience ◽  
Relevant Research ◽  
Fresh Insight ◽  
Insight Into

The following brief survey considers various manoeuvres which can be applied to manipulate the immune response to parasitic infectionsin vivo. The examples quoted largely concern malaria, babesiosis, schistosomiasis and leishmaniasis, predominantly in inbred mouse strains. Since my own relevant research experience has been restricted to leishmaniasis, this will receive undue emphasis, although it does illustrate particularly well points I wish to stress. The types of intervention described do not all provide the precision of interpretation with which they are sometimes credited. Thus, effects of immunosuppression or T-cell depletion alone can usually only implicate the specific immune response (in its broad sense) in shaping the natural history and outcome of an infection or in underlying the effect of prophylactic immunization. Nevertheless, more precise delineation of lymphocyte subset involvement can be obtained by cell replacement studies in some of these models or by exclusion of antibody. The outcomes of these approaches have been (or are) predictable in most cases. More fascinating, however, are the various instances which will be stressed where totally unpredicted and contrary observations have been made which led (or may lead) to fresh insight into the disease. These serendipitous findings illustrate at the same time the value of applying the manoeuvres, even though they imply that the logical immunologist cannot yet always outsmart the parasite by design.

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.

Introduction and Overview

2016 ◽  
Author(s):  
Kenneth J. Sher ◽  
Alvaro Vergés
Keyword(s):  
Substance Use ◽  
Genetic Variation ◽  
Substance Use Disorders ◽  
Drugs Of Abuse ◽  
Psychological Processes ◽  
Cultural Contexts ◽  
Fundamental Nature ◽  
Chronic Effects ◽  
Multidisciplinary Perspective ◽  
Acute And Chronic Effects

Substance use and substance use disorders (SUDs) have been documented in a number of cultures since the beginnings of recorded time and represent major societal concerns in the present day. The chapters in this Handbook review a number of different areas of inquiry into the fundamental nature of substance use and SUDs, their features, their causes, their consequences, their course, their treatment, and their prevention. It is clear that understanding these various aspects of substance use and SUDs requires a multidisciplinary perspective that considers the pharmacology of drugs of abuse, genetic variation in these acute and chronic effects, and psychological processes in the context of the interpersonal and cultural contexts. This chapter provides a general overview of most (but not all) of the topics covered in the Handbook, guiding the reader to the relevant chapters that address each topic in more detail.

Spirituality, Religiosity and Addiction Recovery: Current Perspectives

2019 ◽  
Vol 11 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Livia Beraldo ◽  
Felipe Gil ◽  
Antonio Ventriglio ◽  
Arthur G. de Andrade ◽  
Antonio Geraldo da Silva ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Prospective Studies ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Public Health Problem ◽  
Mediation Effect ◽  
Opioid Use ◽  
Important Public Health Problem ◽  
Positive Effects

Substance use disorders are an important public health problem with a multifactorial etiology and limited effective treatment options. Within this context, spirituality-based approaches may provide interesting and useful options in managing substance use disorders. This kind of intervention can have positive effects in alleviating some core symptoms associated with substance use, such as aggressiveness. Improvement in cessation rates for alcohol, cocaine and opioid use disorders have also been described in some clinical studies. However, spirituality may not play a beneficial role in some subgroups, such as among individuals with crack cocaine and cannabis use disorders. A widely available intervention for alcohol use disorders is Alcoholics Anonymous (AA), which can be seen as a spirituality-based intervention. Spirituality also seems to be especially beneficial for minorities such as Latinos, African-Americans and Native-Americans. Moreover, spiritual-based interventions are also helpful alternatives in many rural environments where conventional healthcare for substance use disorders may not be easily available. However, spiritual-based interventions may be considered as a possible adjunctive therapeutic option to conventional treatments. There is a need for prospective studies outside U.S., especially where spiritual-based approaches are available. It may be difficult to carry out randomized controlled trials because of the nature of the spiritual/ religious dimensions. However, prospective studies that evaluate mediation effect of spirituality and religiosity on recovery would be helpful. Qualitative studies combined with quantitative design offer excellent options to evaluate the recovery process, especially among special populations.

Epigenetic and genetic factors affect transgene methylation imprinting

Development ◽  
1989 ◽  
Vol 107 (1) ◽  
pp. 165-168 ◽  
Author(s):  
C. Sapienza ◽  
J. Paquette ◽  
T.H. Tran ◽  
A. Peterson
Keyword(s):  
Dna Methylation ◽  
Genetic Factors ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Maternal Genome ◽  
Two Factors ◽  
In Trans ◽  
In Cis ◽  
Transgene Locus

In some lines of transgenic mice, the methylation of MspI sites within or adjacent to the transgene locus is affected by the sex of the parent from which the transgene is inherited. These differences are consistent with a role for DNA methylation in genome imprinting. In a previous report, we noted that in one such line, all offspring of females exhibited hypermethylation of the transgene while only some offspring of males carried a hypomethylated transgene. In this report, we provide evidence that this phenomenon is controlled by at least two factors, one of which acts in cis and is dependent on the transgene locus, and one of which acts in trans and is supplied by the maternal genome. We also provide evidence that there are genetic differences between inbred mouse strains in the trans-acting factor.

scholarly journals Multiple genome viewer (MGV): a new tool for visualization and comparison of multiple annotated genomes

2021 ◽  
Author(s):  
Joel E. Richardson ◽  
Richard M. Baldarelli ◽  
Carol J. Bult
Keyword(s):  
Comparative Genomics ◽  
Inbred Mouse ◽  
Mouse Genetics ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Multiple Genome ◽  
Link Type ◽  
Genome Viewer ◽  
Genome Features ◽  
Genome Annotations

AbstractThe assembled and annotated genomes for 16 inbred mouse strains (Lilue et al., Nat Genet 50:1574–1583, 2018) and two wild-derived strains (CAROLI/EiJ and PAHARI/EiJ) (Thybert et al., Genome Res 28:448–459, 2018) are valuable resources for mouse genetics and comparative genomics. We developed the multiple genome viewer (MGV; http://www.informatics.jax.org/mgv) to support visualization, exploration, and comparison of genome annotations within and across these genomes. MGV displays chromosomal regions of user-selected genomes as horizontal tracks. Equivalent features across the genome tracks are highlighted using vertical ‘swim lane’ connectors. Navigation across the genomes is synchronized as a researcher uses the scroll and zoom functions. Researchers can generate custom sets of genes and other genome features to be displayed in MGV by entering genome coordinates, function, phenotype, disease, and/or pathway terms. MGV was developed to be genome agnostic and can be used to display homologous features across genomes of different organisms.

scholarly journals A QUANTITATIVE ANALYSIS OF THE GENETICS OF RESTING BLOOD LACTIC ACID LEVELS IN MICE

Genetics ◽  
1973 ◽  
Vol 75 (1) ◽  
pp. 191-198
Author(s):  
Patricia L Hatchell ◽  
James W MacInnes
Keyword(s):  
Lactic Acid ◽  
Genetic Factors ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Environment Interaction ◽  
Genotype X Environment ◽  
Generation Means ◽  
Nonallelic Interactions ◽  
Lactate Levels

ABSTRACT Resting blood lactate levels were measured in inbred mouse strains, their F1, and several of their segregating generations to determine whether the level of lactic acid is influenced by genetic factors. The inbred strains in each of the two sets used differed significantly from one another for this character. Only one strain showed a significant sex difference. The data could not be fully analyzed because of the failure to fulfill Mather's first criterion for an adequate scale. Nonallelic interactions, in particular, additive x dominance and dominance x dominance, were found to influence the generation means. Genotype x environment interaction was detected and eliminated by log transformation. Negative heterosis was exhibited by all but one noninbred generation.—The data suggest that genes influencing the character are dispersed between the parental lines and that interactions are predominantly of the duplicate kind. A buffering system by which lactate levels are kept at a minimum is proposed.

scholarly journals Analysis of Structural Variation Among Inbred Mouse Strains Identifies Genetic Factors for Autism-Related Traits

2021 ◽  
Author(s):  
Ahmed Arslan ◽  
Zhuoqing Fang ◽  
Meiyue Wang ◽  
Zhuanfen Cheng ◽  
Boyoung Yoo ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Sequence Data ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Autism Spectrum ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Genetic Traits ◽  
Long Read ◽  
Short Read Sequence

AbstractThe genomes of six inbred strains were analyzed using long read (LR) sequencing. The results revealed that structural variants (SV) were very abundant within the genome of inbred mouse strains (4.8 per gene), which indicates that they could impact genetic traits. Analysis of the relationship between SNP and SV alleles across 53 inbred strains indicated that we have a very limited ability to infer whether SV are present using short read sequence data, even when nearby SNP alleles are known. The benefit of having a more complete map of the pattern of genetic variation was demonstrated by identifying at least three genetic factors that could underlie the unique neuroanatomic and behavioral features of BTBR mice that resemble human Autism Spectrum Disorder (ASD). Similar to the genetic findings in human ASD cohorts, the identified BTBR-unique alleles are very rare, and they cause high impact changes in genes that play a role in neurodevelopment and brain function.

scholarly journals High Throughput Computational Mouse Genetic Analysis

2020 ◽  
Author(s):  
Ahmed Arslan ◽  
Yuan Guan ◽  
Xinyu Chen ◽  
Robin Donaldson ◽  
Wan Zhu ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Mitochondrial Targeting ◽  
Phenotypic Data ◽  
Factors Affecting ◽  
Wide Range ◽  
Allelic Differences

AbstractBackgroundGenetic factors affecting multiple biomedical traits in mice have been identified when GWAS data, which measured responses in panels of inbred mouse strains, was analyzed using haplotype-based computational genetic mapping (HBCGM). Although this method was previously used to analyze one dataset at a time; but now, a vast amount of mouse phenotypic data is now publicly available, which could enable many more genetic discoveries.ResultsHBCGM and a whole genome SNP map covering 43 inbred strains was used to analyze 8300 publicly available datasets of biomedical responses (1.52M individual datapoints) measured in panels of inbred mouse strains. As proof of concept, causative genetic factors affecting susceptibility for eye, metabolic and infectious diseases were identified when structured automated methods were used to analyze the output. One analysis identified a novel genetic effector mechanism; allelic differences within the mitochondrial targeting sequence affected the subcellular localization of a protein. We also found allelic differences within the mitochondrial targeting sequences of many murine and human proteins, and these could affect a wide range of biomedical phenotypes.ImplicationsThese initial results indicate that genetic factors affecting biomedical responses could be identified through analysis of very large datasets, and they provide an early indication of how this type of ‘augmented intelligence’ can facilitate genetic discovery.

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