Inbred rat heredity and sex affect oral oxycodone self-administration and augmented intake in long sessions: correlations with anxiety and novelty-seeking

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0314777 - e0314777

Опубликована: Март 10, 2025

Oxycodone abuse frequently begins with prescription oral oxycodone, yet vulnerability factors (e.g. sex, genetics) determining are largely undefined. We evaluated genetic in a rat model of oxycodone self-administration (SA): increasing concentration/session (0.025-0.1mg/ml; 1-, 4-, and 16-h) followed by extinction reinstatement. Active licks intake were greater females than males during 4-h 16-h sessions (p < 0.001). Both sexes increased between 2e-16), but subset strains augmented at = 0.0005). Heritability ( h 2 ) active dose ranged from 0.30 to 0.53. Under progressive ratio (PR) schedule, breakpoints strain-dependent 2e-16). Cued reinstatement was Naive rats assessed using elevated plus maze (EPM), open field (OF), novel object interaction (NOI) tests. correlated these behaviors 28 parameters SA. Anxiety-defining EPM traits most associated SA both sexes, whereas OF NOI more males. Sex heredity major determinants motivation take seek oxycodone; augments dramatically extended access specific strains; anxiety correlates multiple across strains.

Язык: Английский

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Transcriptomics in the era of long-read sequencing

Nature Reviews Genetics, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Язык: Английский

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The evolutionary history of wild and domestic brown rats ( Rattus norvegicus )

Science, Год журнала: 2024, Номер 385(6715), С. 1292 - 1297

Опубликована: Сен. 19, 2024

The brown rat ( Rattus norvegicus ) occupies nearly every terrestrial habitat with a human presence and is one of our most important model organisms. Despite this prevalence, gaps remain in understanding the evolution commensalism, their global dispersal, mechanisms underlying contemporary adaptations to diverse environments. In Review, we explore recent advances evolutionary history rats discuss key challenges, including finding accurately dating historical specimens, disentangling histories multiple domestication events, synthesizing functional variation wild populations development laboratory strains. Advances zooarchaeology population genomics will usher new golden age research on biology rats, positive feedbacks use as biomedical models.

Язык: Английский

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Establishing the hybrid rat diversity program: a resource for dissecting complex traits

Mammalian Genome, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Rat models have been a major model for studying complex disease mechanisms, behavioral phenotypes, environmental factors, and drug development discovery. Inbred rat strains control genetic background allow repeated, reproducible, cellular whole animal phenotyping. The Hybrid Diversity Panel (HRDP) was designed to be powerful panel of inbred rats with genomic, physiological, data serve as resource systems genetics. HRDP consists 96-98 aimed maximize power detect specific loci associated traits while maximizing the diversity among strains. 32-34 genetically diverse two panels recombinant panels. To establish program, embryo resuscitation breeding were done colonies distribution. Whole genome sequencing performed achieve 30X coverage. Genomic, phenotype, strain information is available through Portal at Genome Database ( http://rgd.mcw.edu ).

Язык: Английский

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Genetic Modulation of Protein Expression in Rat Brain

iScience, Год журнала: 2025, Номер 28(3), С. 112079 - 112079

Опубликована: Фев. 21, 2025

Язык: Английский

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An extended miRNA repertoire in Rattus norvegicus

Frontiers in Bioinformatics, Год журнала: 2025, Номер 5

Опубликована: Март 10, 2025

MicroRNAs (miRNAs) are small, non-coding RNA molecules, approximately 22 nucleotides in length, that play crucial roles the regulation of gene expression. They function primarily by binding to complementary sequences 3' untranslated regions (UTRs) target messenger RNAs (mRNAs), leading mRNA degradation or translational repression (Bartel, 2004;Bushati and Cohen, 2007). Through this mechanism, miRNAs involved various biological processes, including development, differentiation, proliferation, apoptosis (Ambros, 2004). The importance as regulatory elements is furthermore emphasized their involvement diseases, particularly cancer, where they can act either oncogenes tumor suppressors (Budakoti et al., 2021;Hussen 2021).MicroRNAs transcribed primary (pri-miRNAs) processed into precursor (pre-miRNAs), which typically around 70 long form hairpin structures 2004).The miRNA duplex generated from precursor, consisting a guide strand (mature miRNA) passenger (mature*). mature incorporated RNA-induced silencing complex (RISC) silencing, while mature* usually degraded, although some cases, it may also be functional 2004;Okamura 2007).Despite critical functions, there significant discrepancy annotation between different model species, notably rat (Rattus norvegicus) mouse (Mus musculus). This arises due differences sequencing efforts strategies but through lineage-specific retroposons playing an essential role birth new genes (Lehnert 2011). Addressing gap for leveraging organism biomedical research, given its widespread use pharmacology toxicology studies (Jacob Kwitek, 2002).In study, we corrected several incorrect homology assignments identified annotated novel miRNAs. Expanding repertoire will enhance utility, toxicological applications, precise networks understanding molecular basis toxicity drug responses.To identify miRNAs, utilized MIRfix curated whole family covariance models described previously (Yazbeck 2019). We focused on families contained at least one mammalian sequence. building was based miRBase version 21 (Kozomara Griffiths-Jones, 2014).We employed infernal v1. 1.3 (Nawrocki Eddy, 2013) scan genome (Rnor 6.0; Ensembl Release 102, accession number GCA 000001895.4) potential candidates using default parameters. chose Rnor 6.0 reference since relies assembly annotations, ensuring comparability with existing datasets. candidate were then subjected series stringent filtering steps ensure accuracy relevance sequences: (1) Candidates filtered e-value cutoff 0.01 bit score threshold 33, following recommendations tutorial (log2(2 * size). ( 2) Duplicated located unfinished chromosomes eliminated. (3) overlapping repeats RepeatMasker excluded (Smit 2013(Smit -2015)). 4) reverse complements smaller excluded.The remaining alignments, included newly candidates. followed additional manual curation alignments involving check sequence conservation and/or assessment ability fold secondary structure.Potential manually assigned names accordance homologous Finally, again blasted against 6.0) extract genomic coordinates blastnfoot_0 . To compatibility newer For our scan, 781 (excluding singletons), 435 already distributed across 247 families. resulted total 449 417 scattered over 459 families.Following procedure eliminate duplicates chromosomes, overlaps repeats, complements, 3521 within 186 three most accounted nearly 2500 those sequences. These contain large numbers (up 59 MIPF0000316), hence introducing substantial variability. circumstance leads detection high each sequence, conducted analysis correction. Additionally, further refine set. final set Rattus norvegicus 55 Notably, 39 no had been rat.With these discoveries, updated rats now contains 548 341 10 require renaming assignments, detailed Table 1. An example interesting requiring featuring illustrated Figure 1(A,B).Initially, extended provide more comprehensive layer case study aiming demonstrate benefits multi-omics data integration part CEFIC LRI C5 -XomeTox projectfoot_1 As larger project, short RNA-Seq libraries 75 rats, examining both thyroid liver tissuesfoot_2 A description methods used published elsewhere (Canzler 2024).Using repertoire, analyzed support all distinct samples. discovered 37 reads tissues. Specifically, 35 read 32 counts individual varied significantly, ranging few thousand per sample, 1(C). When detected tissues, generally comparable.In summary, expands known identifying correcting misannotated By bridging enhanced dataset, includes families, improves utility model. advancements facilitate transcriptomic analyses, miRNA-regulated pathways assessing responses, such after exposure toxins drugs. ((((..((((((((..(((.(((((((..((((.. rno-mir-365-2 listed rno-mir-365 needs renamed. Distinct nucleotide stem region two subtypes indicated above respective column, numbered 1 6. (B) Consensus structure miR-365 containing 48 subtypes. Nucleotide highlighted digits visualized R2R tool (Weinberg Breaker, (C) Support reads. During XomeTox specific tissues: 2024)). Each boxplot summarizes tissues log scale..............)))).))))))).))).))))))))..))))... // R G U C Y

Язык: Английский

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Perinatal Fentanyl Exposure Drives Enduring Addiction Risk and Central Amygdala Gene Dysregulation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

The use of fentanyl and other opioids during pregnancy is a pressing public health issue due to its association with Neonatal Opioid Withdrawal Syndrome (NOWS) long-term neurobehavioral deficits. Human epidemiologic studies are confounded by both genetic environmental factors that differ between exposed unexposed children. We developed novel rat model perinatal exposure characterize NOWS symptoms investigate enduring behavioral molecular outcomes. Offspring born fentanyl-exposed dams exhibited reduced survival, lower body weight, spontaneous withdrawal symptoms, mechanical hypersensitivity. In adolescence, these rats displayed negative affect, while in adulthood, they showed increased self-administration, heightened drug-seeking reinstatement, elevated corticosterone levels withdrawal. To explore the underpinnings physiological outcomes, we conducted RNA-seq central amygdala adult rats, revealing dysregulated pathways related GPCR signaling, adaptive immune response neurodevelopmental processes. These transcriptional changes provide insights into mechanisms driving addiction vulnerability stress-related behaviors following early exposure. Our findings highlight lasting impact opioid an experimental system avoids many confounds plague humans, underscoring need for preclinical models study consequences. This offers translational relevance developing therapeutic strategies mitigate reduce neuropsychiatric risks associated prenatal

Язык: Английский

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Pangenome reconstruction in rats enhances genotype-phenotype mapping and novel variant discovery

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 11, 2024

The HXB/BXH family of recombinant inbred rat strains is a unique genetic resource that has been extensively phenotyped over 25 years, resulting in vast dataset quantitative molecular and physiological phenotypes. We built pangenome graph from 10x Genomics Linked-Read data for 31 rats to study variation association mapping. includes 0.2Gb sequence not present the reference mRatBN7.2, confirming capture substantial additional variation. validated variants challenging regions, including complex structural resolving into multiple haplotypes. Phenome-wide analysis SNPs uncovered associated with glucose/insulin levels hippocampal gene expression. propose an interaction between

Язык: Английский

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Y and Mitochondrial Chromosomes in the Heterogeneous Stock Rat Population

G3 Genes Genomes Genetics, Год журнала: 2024, Номер 14(11)

Опубликована: Сен. 9, 2024

Abstract Genome-wide association studies typically evaluate the autosomes and sometimes X Chromosome, but seldom consider Y or mitochondrial (MT) Chromosomes. We genotyped MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. identified distinct 4 among founders. However, only 2 types of each nonrecombinant chromosome were observed our modern HS rat (generations 81–97). Despite relatively large sample size, there virtually no significant associations for behavioral, physiological, metabolome, microbiome traits after correcting multiple comparisons. both strongly associated with expression a few genes located on those chromosomes, which provided positive control. Our results suggest that within are differences influence behavioral physiological traits. These do not address other ancestral appear rats, nor they effects may exist populations, species.

Язык: Английский

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Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding

Genome Research, Год журнала: 2024, Номер 34(11), С. 2081 - 2093

Опубликована: Ноя. 1, 2024

We report the construction and analysis of a new reference genome assembly for Rattus norvegicus , laboratory rat, widely used experimental animal model organism. The has been adopted as rat by Genome Reference Consortium is named GRCr8. employed 40× Pacific Biosciences (PacBio) HiFi sequencing coverage scaffolding using optical mapping Hi-C. genomic DNA from male BN/NHsdMcwi (BN) same strain colony prior assembly, mRatBN7.2. at chromosome level with 98.7% sequence assigned to chromosomes. All chromosomes have increased in size compared k -mer indicates that subject fully inbred represented single haploid assembly. Notable increases are observed Chromosomes 3, 11, 12 prospective rDNA regions. In addition, Chr Y threefold more consistent karyotype than previous assemblies. Several other grown incorporation sizable discrete blocks. These contain highly repetitive sequences encode numerous previously unannotated genes. centromeric incorporated most annotation performed NCBI RefSeq, which confirms improvement quality adds 1100 protein coding PacBio Iso-Seq data acquired multiple tissues released concurrently aid further analyses.

Язык: Английский

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