BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity

Martins, Airton C.; López-Granero, Caridad; Ferrer, Bertha Beatriz Socarrás; Tinkov, Alexey A.; Skalny, Anatoly V.; Paoliello, Mônica Maria Bastos; Aschner, Michael

doi:10.3390/biom11121762

Cited by 9 publications

(8 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies using BXD recombinant inbred (RI) mice investigated genes that are associated with alcohol sensitivity and a predisposition to alcoholism to understand the underlying mechanisms of neurotoxicity in response to ethanol [ 79 ]. In evaluations of the genetic susceptibility to ethanol consumption and withdrawal, strains showed contrasting behavioral responses to ethanol, since the BXD RI strains showed that C57BL/6J (B6) inbred mice were able to drink large amounts of ethanol voluntarily, while DBA/2J (D2) mice showed improved withdrawal to acute ethanol [ 80 ].…”

Section: Resultsmentioning

confidence: 99%

Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review

2022

View full text Add to dashboard Cite

Alcohol use disorder (AUD) is a highly prevalent, comorbid, and disabling disorder. The underlying mechanism of ethanol neurotoxicity and the involvement of oxidative stress is still not fully elucidated. However, ethanol metabolism has been associated with increased oxidative stress through alcohol dehydrogenase, the microsomal ethanol oxidation system, and catalase metabolic pathways. We searched the PubMed and genome-wide association studies (GWAS) catalog databases to review the literature systematically and summarized the findings focusing on AUD and alcohol abstinence in relation to oxidative stress. In addition, we reviewed the ClinicalTrials.gov resource of the US National Library of Medicine to identify all ongoing and completed clinical trials that include therapeutic interventions based on antioxidants. The retrieved clinical and preclinical studies show that oxidative stress impacts AUD through genetics, alcohol metabolism, inflammation, and neurodegeneration.

show abstract

Section: Resultsmentioning

confidence: 99%

Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review

2022

View full text Add to dashboard Cite

show abstract

“…However, major questions persist about the association of cardiac Cu concentrations with heart morphology and function and its underlying genetic regulation. To this end, we have previously applied a systems genetics approach using the BXD family of RI mice, a murine GRP that has previously been successfully used for several QTL analyses to identify candidate genes and gene networks that underlie the effects of trace metals in the brain ( 34 , 35 ). Similarly, in the current study, we showed that the cardiac Cu concentration in BXD mice is significantly correlated with various echocardiographic parameters.…”

Section: Discussionmentioning

confidence: 99%

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice

Bajpai

Orgil

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundCopper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism. However, the genetic basis underlying cardiac Cu levels and their effects on heart traits remain to be understood. Representing the largest murine genetic reference population, BXD strains have been widely used to explore genotype-phenotype associations and identify quantitative trait loci (QTL) and candidate genes.MethodsCardiac Cu concentration and heart function in BXD strains were measured, followed by QTL mapping. The candidate genes modulating Cu homeostasis in mice hearts were identified using a multi-criteria scoring/filtering approach.ResultsSignificant correlations were identified between cardiac Cu concentration and left ventricular (LV) internal diameter and volumes at end-diastole and end-systole, demonstrating that the BXDs with higher cardiac Cu levels have larger LV chamber. Conversely, cardiac Cu levels negatively correlated with LV posterior wall thickness, suggesting that lower Cu concentration in the heart is associated with LV hypertrophy. Genetic mapping identified six QTLs containing a total of 217 genes, which were further narrowed down to 21 genes that showed a significant association with cardiac Cu content in mice. Among those, Prex1 and Irx3 are the strongest candidates involved in cardiac Cu modulation.ConclusionCardiac Cu level is significantly correlated with heart chamber size and hypertrophy phenotypes in BXD mice, while being regulated by multiple genes in several QTLs. Prex1 and Irx3 may be involved in modulating Cu metabolism and its downstream effects and warrant further experimental and functional validations.

show abstract

“…(3) a strain often crossed with C57BL/6J that is used for studying genotype-phenotype interactions (Geisert and Williams, 2020;Martins et al, 2021;Sasani et al, 2022); and (4) numerous other models which contain unique phenotypes due to genetic background, such as the PWD/PhJ strain, a mouse historically utilized to model hybrid sterility (Chubb and Nolan, 1987;Lustyk et al, 2019). The resulting SV calls can be used for identifying variants associated with disease and to study large segments of DNA which were hidden from previous genomic studies.…”

Section: Discussionmentioning

confidence: 99%

“…We characterized and sequence-resolved genome wide SVs present in 20 laboratory mouse strains with longread sequencing technology. This cohort represents various popular research models such as: (1) the parental founders of the CC and DO crosses, which are powerful selective breeding panels used for trait mapping (Iraqi et al, 2008); (2) six resultant CC strains which have interesting phenotypes; (3) a strain often crossed with C57BL/6J that is used for studying genotype-phenotype interactions (Geisert and Williams, 2020; Martins et al, 2021; Sasani et al ., 2022); and (4) numerous other models which contain unique phenotypes due to genetic background, such as the PWD/PhJ strain, a mouse historically utilized to model hybrid sterility (Chubb and Nolan, 1987; Lustyk et al, 2019). The resulting SV calls can be used for identifying variants associated with disease and to study large segments of DNA which were hidden from previous genomic studies.…”

Section: Discussionmentioning

confidence: 99%

Resolution of structural variation in diverse mouse genomes reveals chromatin remodeling due to transposable elements

Ferraj

Audano

Balachandran

et al. 2022

Preprint

View full text Add to dashboard Cite

Diverse inbred mouse strains are among the foremost models for biomedical research, yet genome characterization of many strains has been fundamentally lacking in comparison to human genomics research. In particular, the discovery and cataloging of structural variants is incomplete, limiting the discovery of potentially causative alleles for phenotypic variation across individuals. Here, we utilized long-read sequencing to resolve genome-wide structural variants (SVs, variants ≥ 50 bp) in 20 genetically distinct inbred mice. We report 413,758 site-specific SVs that affect 13% (356 Mbp) of the current mouse reference assembly, including 510 previously unannotated variants which alter coding sequences. We find that 39% of SVs are attributed to transposable element (TE) variation accounting for 75% of bases altered by SV. We then utilized this callset to investigate the impact of TE heterogeneity on mouse embryonic stem cells (mESCs), and find multiple TE classes that influence chromatin accessibility across loci. We also identify strain-specific transcription start sites originating in polymorphic TEs that modify gene expression. Our work provides the first long-read based analysis of mouse SVs and illustrates that previously unresolved TEs underlie epigenetic and transcriptome differences in mESCs.

show abstract

BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity

Cited by 9 publications

References 88 publications

Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review

Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice

Resolution of structural variation in diverse mouse genomes reveals chromatin remodeling due to transposable elements

Contact Info

Product

Resources

About