The dihydropyrimidine dehydrogenase gene contributes to heritable differences in sleep in mice

Keenan, Brendan T.; Galante, Raymond J.; Zhang, Lin; Guo, Xiaofeng; Veatch, Olivia J.; Chesler, Elissa J.; O’Brien, William T.; Svenson, Karen L.; Churchill, Gary A.

doi:10.1016/j.cub.2021.09.049

Cited by 8 publications

(5 citation statements)

References 91 publications

(131 reference statements)

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“…Thirty-two genes are predicted as essential genes based on the grRatio filter and experimental evidence of knockout studies. The details of essential variant genes are given in Supplementary Table S4 ([ 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]). Most of these genes are part of metabolic processes and energy demands of the brain.…”

Section: Resultsmentioning

confidence: 99%

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Sneha,

Dharshini,

Taguchi

et al. 2023

Genes

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Huntington’s disease (HD) is a progressive neurodegenerative disorder caused due to a CAG repeat expansion in the huntingtin (HTT) gene. The primary symptoms of HD include motor dysfunction such as chorea, dystonia, and involuntary movements. The primary motor cortex (BA4) is the key brain region responsible for executing motor/movement activities. Investigating patient and control samples from the BA4 region will provide a deeper understanding of the genes responsible for neuron degeneration and help to identify potential markers. Previous studies have focused on overall differential gene expression and associated biological functions. In this study, we illustrate the relationship between variants and differentially expressed genes/transcripts. We identified variants and their associated genes along with the quantification of genes and transcripts. We also predicted the effect of variants on various regulatory activities and found that many variants are regulating gene expression. Variants affecting miRNA and its targets are also highlighted in our study. Co-expression network studies revealed the role of novel genes. Function interaction network analysis unveiled the importance of genes involved in vesicle-mediated transport. From this unified approach, we propose that genes expressed in immune cells are crucial for reducing neuron death in HD.

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Section: Resultsmentioning

confidence: 99%

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Sneha,

Dharshini,

Taguchi

et al. 2023

Genes

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“…Data supports the theory that β‐alanine is a neurotransmitter promoting mice sleep. [ 83 ] β‐alanine supplements improve energy metabolism without any associated side effects. [ 84 ] High doses of β‐alanine intake during intense military training may reduce interleukin‐10 levels and play a therapeutic role by regulating inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Dihydropyrimidine dehydrogenase encodes the rate‐limiting enzyme in the metabolic pathway that decomposes uracil and thymine into β‐alanine. [ 83 ] Uracil and D‐ribose form uridine, a component of RNA (ribonucleic acid). Uridine plays a role in the glycolysis pathway of galactose.…”

Section: Discussionmentioning

confidence: 99%

Systematic Metabolic Profiling of Mice with Sleep‐Deprivation

Si,

Sun,

Liang

et al. 2023

Advanced Biology

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Adequate sleep is essential for the biological maintenance of physical energy. Lack of sleep can affect thinking, lead to emotional anxiety, reduce immunity, and interfere with endocrine and metabolic processes, leading to disease. Previous studies have focused on long‐term sleep deprivation and the risk of cancer, heart disease, diabetes, and obesity. However, systematic metabolomics analyses of blood, heart, liver, spleen, kidney, brown adipose tissue, and fecal granules have not been performed. This study aims to systematically assess the metabolic changes in the target organs caused by sleep deprivation in vivo, to search for differential metabolites and the involved metabolic pathways, to further understand the impact of sleep deprivation on health, and to provide strong evidence for the need for early intervention.

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“…WDIS have been strategically utilized in gene mapping studies to introduce increased diversity [12][13][14][15][16], profiled in immunological [17], metabolic [18], and reproductive studies [19][20][21], and featured as founders to current mouse diversity populations such as the Collaborative Cross (CC) and Diversity Outbred (DO; [22,23]). Indeed, the majority of quantitative trait loci (QTL) identified in mapping studies in the CC and DO are attributable to the allelic effects of one or more of the three wild-derived founder haplotypes [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models

Dumont,

Gatti,

Ballinger

et al. 2024

PLoS Genet

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The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for over a century. However, laboratory mice capture only a subset of the genetic variation found in wild mouse populations, ultimately limiting the potential of classical inbred strains to uncover phenotype-associated variants and pathways. Wild mouse populations are reservoirs of genetic diversity that could facilitate the discovery of new functional and disease-associated alleles, but the scarcity of commercially available, well-characterized wild mouse strains limits their broader adoption in biomedical research. To overcome this barrier, we have recently developed, sequenced, and phenotyped a set of 11 inbred strains derived from wild-caught Mus musculus domesticus. Each of these “Nachman strains” immortalizes a unique wild haplotype sampled from one of five environmentally distinct locations across North and South America. Whole genome sequence analysis reveals that each strain carries between 4.73–6.54 million single nucleotide differences relative to the GRCm39 mouse reference, with 42.5% of variants in the Nachman strain genomes absent from current classical inbred mouse strain panels. We phenotyped the Nachman strains on a customized pipeline to assess the scope of disease-relevant neurobehavioral, biochemical, physiological, metabolic, and morphological trait variation. The Nachman strains exhibit significant inter-strain variation in >90% of 1119 surveyed traits and expand the range of phenotypic diversity captured in classical inbred strain panels. These novel wild-derived inbred mouse strain resources are set to empower new discoveries in both basic and preclinical research.

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The dihydropyrimidine dehydrogenase gene contributes to heritable differences in sleep in mice

Cited by 8 publications

References 91 publications

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Systematic Metabolic Profiling of Mice with Sleep‐Deprivation

Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models

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