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Muscle-specific rescue of Bmal1 impacts survival and health span of the Bmal1-KO mouse

ABSTRACT: This dataset was generated to investigate the muscle and systemic effects of muscle-specific Bmal1 expression in the Bmal1-KO mouse model

ORGANISM(S): Mus musculus

PROVIDER: GSE232957 | GEO | 2024/10/03

REPOSITORIES: GEO

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Muscle-specific rescue of Bmal1 impacts survival and health span of the Bmal1-KO mouse

Project description:Muscle-specific rescue of Bmal1 impacts survival and health span of the Bmal1-KO mouse

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TMT analysis of proteomic changes in the gastrocnemius skeletal muscles of WT and Bmal1-KO mice, and Bmal1-KO mice rescued with AAV-mediated muscle-specific expression of Bmal1.

Project description:TMT analysis of proteomic changes in the gastrocnemius skeletal muscles of WT and Bmal1-KO mice, and Bmal1-KO mice rescued with AAV-mediated muscle-specific expression of Bmal1.

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Proteomics analysis of regulation by Bmal1 and physiological time-restricted feeding

Project description:To define regulation of tissue proteomes by Bmal1, daily feeding rhythm, and the interaction, we employed Bmal1-stopFL mice, which do not express the main transcriptional activator of the molecular clock, Bmal1, except in cre recombinase-expressing cells1,2 (Figure 1A). Bmal1-stopFL mice lacking cre (Bmal1 knockout, KO) are analogous to Bmal1-null mice and display severely impaired behavioral and molecular rhythms1-3. Hepatocyte-specific Alfp-cre and skeletal muscle-specific Hsa-cre genes were introduced to generate a single line wherein both hepatocyte and skeletal muscle Bmal1 were reconstituted (Liver+Muscle-RE), i.e., rescued (Smith, Koronowski et al. 2023). This approach had the benefit of analyzing liver and muscle from the same mice but comes with the qualification that the abundance of some proteins may be influenced by Bmal1 function in the other tissue, or by a synergistic effect of Bmal1 in both tissues, rather than through rescue of local Bmal1 function alone. Proteomic anlaysis was performed in liver and skeletal muscle.

2024-01-26 | PXD040362 | Pride

Liver Circadian RNA-Seq from WT and Bmal1 muscle-specific KO (mKO) mice

Project description:Transcriptomic analysis to reveal the impact of muscle-specific Bmal1 knockout on daily cycles of gene expression in the liver

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LC-MS/MS identification of BMAL1 interaction proteins

Project description:Advances in circadian research revealed an intricate relationship between aging and circadian rhythms. However, whether and how the circadian machinery contribute to stem cell aging, especially in primates, remains poorly understood. In this study, we investigated the role of BMAL1, the only non-redundant circadian clock component, during aging in mesenchymal progenitor cells (MPCs). We observed an accelerated aging phenotype in both BMAL1 deficient human and cynomolgus monkey MPCs. Notably, this phenotype is mainly attributed to a transcriptional-independent role of BMAL1 in stabilizing the heterochromatin and thus preventing LINE1 activation. In senescent MPCs from human and cynomolgus monkeys, dampened LINE1 binding capacity of BMAL1 and synergistically activated LINE1 transcripts were observed. Furthermore, similar de-stabilized heterochromatin and aberrant LINE1s transcription was observed in the skin and muscle tissues from BMAL1-deficient cynomolgus monkey. Altogether, these findings uncover a noncanonical role of BMAL1 in stabilizing heterochromatin to inactivate LINE1 that drives aging in primates.

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Circadian transcriptome of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO and control Cre- littermates

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Project description:Obesity and liver diseases are associated with the disruption of the circadian clock that orchestrates mammalian physiology to optimize nutrient metabolism and storage. We show here that the activity of the circadian clock regulator BMAL1 is perturbed during liver fibrosis in humans. To understand the impact of BMAL1 perturbation in obesity and liver diseases, we assessed the impact of a high fat diet or leptin deficiency on Bmal1 knockout mice. While Bmal1 knockout mice were prone to obesity, they were protected against insulin resistance, hepatic steatosis, inflammation, and fibrosis. In addition to direct transcriptional regulation of metabolic programs by BMAL1, we show that adaptation of the growth hormone and sex hormone pathways plays a critical role in this protection. Similar endocrine perturbations correlate with the development of liver fibrosis in humans, suggesting that endocrine perturbation associated with circadian disruption is critical for the pathogenesis of metabolic and liver diseases.

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Transcriptomic analysis of cortex tissue from neuron-specific Bmal1 KO mice

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2023-08-23 | GSE241218 | GEO

Loss of skeletal muscle Bmal1 +/- Acute Exercise

Project description:Investigate the effects loss of skeletal muscle Bmal1 has on the acute transcriptional response to exercise in gastrocnemius muscle.

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Circadian transcriptome of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO and control Cre- littermates

Project description:To investigate the role of the circadian clock gene Bmal1 in skeletal muscle, we compared the circadian transcriptomes of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO (mKO) and their control Cre- littermates (Ctrl). Keyword: Circadian Transcriptome, time course 72 samples were analyzed, comprised of 4 experimental groups (Ctrl SOL, mKO SOL, Ctrl TA, mKO TA), with 3 biological replicates for each time point sampled every 4 hours for 24 hours. SOL and TA muscles were collected from the same animals, as indicated by Source Animal ID data column

2014-01-01 | E-GEOD-43071 | biostudies-arrayexpress

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