POGZ (Pogo transposable element derived with ZNF domain) is known to function as a regulator of gene expression. While variations in the gene have been associated with intellectual disabilities and developmental delays in humans, the exact pathophysiological mechanisms remain unclear. To shed light on this, we created two lines of conditional knockout mice for , one specific to excitatory neurons (Emx1-Pogz mice) and the other to inhibitory neurons (Gad2-Pogz mice) in the brain. Emx1-Pogz mice showed a decrease in body weight, similar to total knockout mice. Although the two lines did not display significant morphological abnormalities in the telencephalon, impaired POGZ function affected the electrophysiological properties of both excitatory and inhibitory neurons differently. These findings suggest that these mouse lines could be useful tools for clarifying the precise pathophysiological mechanisms of neurodevelopmental disorders associated with gene abnormalities.
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http://dx.doi.org/10.3390/cells13060540 | DOI Listing |
Front Biosci (Landmark Ed)
January 2025
Department of Cardiothoracic Surgery, The Affiliated Jiangyin Hospital of Nantong University, 214400 Jiangyin, Jiangsu, China.
Background: This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms.
Methods: Differentially expressed genes between ESCC mouse oesophageal cancer tissues and normal tissues were analysed via RNA-seq; among them, SENP5 expression was upregulated, and this gene was selected for further analysis. Immunohistochemistry and western blotting were then used to validate the increased protein level of SENP5 in both mouse and human ESCC samples.
Front Biosci (Landmark Ed)
January 2025
Department of Biomedical Sciences, Grand Valley State University, Allendale, MI 49401, USA.
Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear.
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January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.
Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.
View Article and Find Full Text PDFViruses
December 2024
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8 T cells without compromising the development of VACV-specific memory CD8 T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8 T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase.
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