173,640 results match your criteria knockout mice

α7 Nicotinic Acetylcholine Receptor Agonists Regulate Inflammation and Growth Hormone Resistance in Sepsis.

Shock 2021 Apr 13. Epub 2021 Apr 13.

Departments of Surgery, State University of New York (SUNY), Upstate Medical University, Syracuse, New York, USA.

Abstract: During sepsis the normal induction of circulating insulin-like growth factor-I (IGF-I) by growth hormone (GH) action on liver is attenuated, a phenomenon called hepatic GH resistance. Hepatic GH resistance can be caused by cytokine-mediated activation of the NF-κB pathway which interferes with normal GH-signaling. The afferent and efferent fibers of the vagus nerve are integral to the cholinergic anti-inflammatory pathway (CAP) which attenuates hepatic TNFα production by activating the α7 nicotinic acetylcholine receptor (α7nAChR). Read More

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MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4.

Pathobiology 2021 Apr 21:1-12. Epub 2021 Apr 21.

Department of Physiology & Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an, China.

Background: The dysregulation of proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the major causes of atherosclerosis (AS). Accumulating studies confirm that Kruppel-like factor 4 (KLF4) can regulate the proliferation and differentiation of VSMCs through multiple signaling pathways. However, the mechanism of KLF4 dysregulation remains unknown. Read More

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Piccolo is essential for the maintenance of mouse retina but not cochlear hair cell function.

Aging (Albany NY) 2021 Apr 21;13. Epub 2021 Apr 21.

School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.

Piccolo is a presynaptic protein with high conservation among different species, and the expression of Piccolo is extensive in vertebrates. Recently, a small fragment of Piccolo (Piccolino), arising due to the incomplete splicing of intron 5/6, was found to be present in the synapses of retinas and cochleae. However, the comprehensive function of Piccolo in the retina and cochlea remains unclear. Read More

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SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility.

Cell Rep 2021 Apr;35(3):109025

School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing 100084, China; Beijing Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address:

Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid β-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. Read More

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Young DAPK1 knockout mice have altered pre-synaptic function.

J Neurophysiol 2021 Apr 21. Epub 2021 Apr 21.

Pharmacology, University of Colorado Anschutz Medical Campus, United States.

The death associated protein kinase 1 (DAPK1) has recently been shown to have a physiological function in long-term depression (LTD) of glutamatergic synapses: Acute inhibition of DAPK1 blocked the LTD that is normally seen at the hippocampal CA1 synapse in young mice, and a pharmacogenetic combination approach showed that this specifically required DAPK1-mediated suppression of post-synaptic CaMKII binding to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B during LTD stimuli. Surprisingly, we found here that genetic deletion of DAPK1 (in DAPK1 mice) did not reduce LTD. Paired pulse facilitation experiments indicated a pre-synaptic compensation mechanism: in contrast to wild type mice, LTD stimuli in DAPK1 mice decreased pre-synaptic release probability. Read More

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SRC-1 Deficiency Increases Susceptibility of Mice to Depressive-Like Behavior After Exposure to CUMS.

Neurochem Res 2021 Apr 21. Epub 2021 Apr 21.

Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear receptors (NRs) when NRs are activated by steroid hormones, such as glucocorticoid. SRC-1 is abundant in hippocampus and hypothalamus and is also related to some major risk factors for depression, implicated by its reduced expression after stress and its effect on hypothalamus-pituitary-adrenal gland axis function. However, whether SRC-1 is involved in the formation of depression remains unclear. Read More

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Liver circadian clock disruption alters perivascular adipose tissue gene expression and aortic function in mice.

Am J Physiol Regul Integr Comp Physiol 2021 Apr 21. Epub 2021 Apr 21.

Medicine, University of Alabama at Birmingham, United States.

The liver plays a central role that influences cardiovascular disease outcomes through regulation of glucose and lipid metabolism. It is recognized that the local liver molecular clock regulates some liver-derived metabolites. However, it is unknown whether the liver clock may impact cardiovascular function. Read More

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Acute stress reveals different impacts in male and female Zdhhc7-deficient mice.

Brain Struct Funct 2021 Apr 20. Epub 2021 Apr 20.

Department of Mental Health, University of Münster, Münster, Germany.

Numerous processes of neuronal development and synaptic plasticity in the brain rely on the palmitoyl acyltransferase ZDHHC7, as it palmitoylates various synaptic and extrasynaptic proteins such as neural cell adhesion molecule (NCAM) or gamma-aminobutyric acid (GABA) receptors. In addition, ZDHHC7 palmitoylates sex steroid hormone receptors and is, therefore, indirectly linked to mental disorders that often occur because of or in conjunction with stress. In this work, we investigated how ZDHHC7 affects stress responses in mice. Read More

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Contribution of growth hormone secretagogue receptor (GHSR) signaling in the ventral tegmental area (VTA) to the regulation of social motivation in male mice.

Transl Psychiatry 2021 Apr 20;11(1):230. Epub 2021 Apr 20.

Department of Neuroscience, Carleton University, Ottawa, ON, Canada.

Most psychiatric disorders are characterized by deficits in the ability to interact socially with others. Ghrelin, a hormone normally associated with the regulation of glucose utilization and appetite, is also implicated in the modulation of motivated behaviors including those associated with food and sex rewards. Here we hypothesized that deficits in ghrelin receptor (growth hormone secretagogue receptor; GHSR) signaling are also associated with deficits in social motivation in male mice. Read More

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Enhanced Ca signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model ( ).

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Department of Nephrology, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany;

Gain-of-function mutations in the gene (encoding the T-type calcium channel Ca3.2) cause autosomal-dominant familial hyperaldosteronism type IV (FH-IV) and early-onset hypertension in humans. We used CRISPR/Cas9 to generate knockin mice as a model of the most common FH-IV mutation, along with corresponding knockout mice ( ). Read More

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Monocyte-Derived Dendritic Cells (moDCs) Differentiate into Bcl6 Mature moDCs to Promote Cyclic di-GMP Vaccine Adjuvant-Induced Memory T Cells in the Lung.

J Immunol 2021 May 19;206(9):2233-2245. Epub 2021 Apr 19.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, FL

Induction of lung mucosal immune responses is highly desirable for vaccines against respiratory infections. We recently showed that monocyte-derived dendritic cells (moDCs) are responsible for lung IgA induction. However, the dendritic cell subset inducing lung memory T cells is unknown. Read More

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STEAP4 expression in CNS resident cells promotes Th17 cell-induced autoimmune encephalomyelitis.

J Neuroinflammation 2021 Apr 20;18(1):98. Epub 2021 Apr 20.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH, USA.

Background: Multiple sclerosis (MS) is a debilitating neurological disease caused by autoimmune destruction of the myelin sheath. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for the pathogenesis of MS. We and others have previously demonstrated that IL-17 is critical for the pathogenesis of EAE. Read More

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Bidirectional interconversion between PtdIns4P and PtdIns(4,5)P is required for autophagic lysosome reformation and protection from skeletal muscle disease.

Autophagy 2021 Apr 20:1-3. Epub 2021 Apr 20.

Cancer Program, and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.

Autophagic lysosome reformation (ALR) recycles autolysosome membranes formed during autophagy, to make lysosomes and is essential for continued autophagy function. Localized membrane remodeling on autolysosomes leads to the extension of reformation tubules, which undergo scission to form new lysosomes. The phosphoinositides phosphatidylinositol-4-phosphate (PtdIns4P) and phosphatidylinositol-4,5-bisphosphate (PtdIns[4,5]P) induce this remodeling by recruiting protein effectors to membranes. Read More

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Hyperreflexia and enhanced ripple oscillations in the taurine-deficient mice.

Amino Acids 2021 Apr 20. Epub 2021 Apr 20.

Center for Developmental Neuroscience, College of Staten Island, 2800 Victory Blvd., Staten Island, NY, 10314, USA.

In this study, we examined neuronal excitability and skeletal muscle physiology and histology in homozygous knockout mice lacking cysteine sulfonic acid decarboxylase (CSAD-KO). Neuronal excitability was measured by intracerebral recording from the prefrontal cortex. Skeletal muscle response was measured through stretch reflex in the ankle muscles. Read More

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Temporal Overexpression of IL-22 and Reg3γ differentially Impacts the Severity of Experimental Autoimmune Encephalomyelitis.

Immunology 2021 Apr 20. Epub 2021 Apr 20.

Erciyes University School of Medicine, Department of Medical Biology, Kayseri, Turkey.

IL-22 is an alpha-helical cytokine which belongs to the IL-10 family of cytokines. IL-22 is produced by RORγt+ innate and adaptive lymphocytes, including ILC3, γδ T, iNKT, Th17, and Th22 cells and some granulocytes. IL-22 receptor is expressed primarily by non-hematopoietic cells. Read More

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Low-dose decitabine modulates T cell homeostasis and restores immune tolerance in immune thrombocytopenia.

Blood 2021 Apr 19. Epub 2021 Apr 19.

Qilu hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Our previous clinical study demonstrated that low-dose decitabine showed sustained responses in nearly half of refractory immune thrombocytopenia (ITP) patients. The long-term efficacy of decitabine in ITP is not likely due to its simple role in increasing platelet production. Whether decitabine has the potential to restore immune tolerance in ITP is unknown. Read More

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Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury.

J Am Soc Nephrol 2021 Apr 19. Epub 2021 Apr 19.

Division of CKD Pathophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Background: The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI). Read More

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MiR-29c downregulates tumor-expressed B7-H3 to mediate the antitumor NK-cell functions in ovarian cancer.

Gynecol Oncol 2021 Apr 17. Epub 2021 Apr 17.

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: B7-H3 is a member of the B7 family of immune checkpoint molecule. Although B7-H3 has been shown to regulate T cell-mediated peripheral immune response, whether it also correlated with NK cell exhaustion in ovarian cancer remains unclear. The purpose of this study was to explore the mechanism of B7-H3 regulating NK-cell proliferation and function. Read More

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Lack of the peroxiredoxin 6 gene causes impaired spatial memory and abnormal synaptic plasticity.

Mol Brain 2021 Apr 19;14(1):72. Epub 2021 Apr 19.

Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.

Peroxiredoxin 6 (PRDX6) is expressed dominantly in the astrocytes and exerts either neuroprotective or neurotoxic effects in the brain. Although PRDX6 can modulate several signaling cascades involving cognitive functions, its physiological role in spatial memory has not been investigated yet. This study aims to explore the function of the Prdx6 gene in spatial memory formation and synaptic plasticity. Read More

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4R-cembranoid confers neuroprotection against LPS-induced hippocampal inflammation in mice.

J Neuroinflammation 2021 Apr 19;18(1):95. Epub 2021 Apr 19.

Department of Biochemistry, Universidad Central del Caribe School of Medicine, Av. Sta. Juanita, Bayamón, 00960, Puerto Rico.

Background: Chronic brain inflammation has been implicated in the pathogenesis of various neurodegenerative diseases and disorders. For example, overexpression of pro-inflammatory cytokines has been associated with impairments in hippocampal-dependent memory. Lipopolysaccharide (LPS) injection is a widely used model to explore the pathobiology of inflammation. Read More

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R-Ras Deficiency in Pericytes Causes Frequent Microphthalmia and Perturbs Retinal Vascular Development.

J Vasc Res 2021 Apr 19:1-15. Epub 2021 Apr 19.

Cancer and Blood Disorders Institute, Institute for Fundamental Biomedical Research, and Department of Surgery, Johns Hopkins All Children's Hospital, and Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, Florida, USA.

Purpose: The retinal vasculature is heavily invested by pericytes. Small GTPase R-Ras is highly expressed in endothelial cells and pericytes, suggesting importance of this Ras homolog for the regulation of the blood vessel wall. We investigated the specific contribution of pericyte-expressed R-Ras to the development of the retinal vasculature. Read More

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Effects of cigarette smoke on the aggravation of ovalbumin-induced asthma and the expressions of TRPA1 and tight junctions in mice.

Mol Immunol 2021 Apr 16;135:62-72. Epub 2021 Apr 16.

School of Traditional Chinese Medicine & Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China.

The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. Read More

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Maternal smoking during pregnancy aggravated muscle phenotype in FHL1 offspring mice similar to congenital clubfoot through P2RX7-mediated pyroptosis.

Toxicol Lett 2021 Apr 16. Epub 2021 Apr 16.

Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China. Electronic address:

Congenital clubfoot (CCF) is a common birth defect. Maternal smoking during pregnancy increases the risk of CCF. In previous research, we found muscle phenotypes similar to CCF in four and a half LIM domain protein 1 (FHLI) offspring mice (FHL1). Read More

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Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice.

Toxicology 2021 Apr 16;456:152785. Epub 2021 Apr 16.

Department of Occupational and Environmental Health, Tokyo University of Science, Noda, Japan. Electronic address:

Acrylamide (ACR), a recognized neurotoxicant in humans and experimental animals, is widely used in industry and in food generated through Maillard reaction. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular defense system and activates antioxidants and cytoprotective genes. The exact roles of Nrf2 in environmental electrophile-induced neurotoxicity is poorly understood. Read More

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Anxiety-like behavior in female mice is modulated by STAT3 signaling in midbrain dopamine neurons.

Brain Behav Immun 2021 Apr 16. Epub 2021 Apr 16.

Centre de Recherche du CHUM. Department of; Nutrition; Montreal Diabetes Research Center; Center for Studies in Behavioural Neurobiology (Concordia University). Electronic address:

The central signalling actions of cytokines are mediated by signal transducer and activator of transcription (STAT3). STAT3 activation plays a pivotal role in the behavioral responses to the adiposity hormone leptin, including in midbrain dopamine (DA) neurons where it mediates the influence of leptin to diminish physical activity and running reward in male mice. Leptin also has anxiolytic effects which have been tied to the mesolimbic DA system. Read More

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Genome wide CRISPR screening reveals a role for sialylation in the tumorigenesis and chemoresistance of acute myeloid leukemia cells.

Cancer Lett 2021 Apr 16. Epub 2021 Apr 16.

Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Aberrant activation of cytokine and growth factor signal transduction pathways confers enhanced survival and proliferation properties to acute myeloid leukemia (AML) cells. However, the mechanisms underlying the deregulation of signaling pathways in leukemia cells are unclear. To identify genes capable of independently supporting cytokine-independent growth, we employed a genome-wide CRISPR/Cas9-mediated loss-of-function screen in GM-CSF-dependent human AML TF-1 cells. Read More

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Regulation of monoamine levels by typical and atypical antipsychotics in Caenorhabditis elegans mutant for Nuclear Distribution Element genes.

Neurochem Int 2021 Apr 16:105047. Epub 2021 Apr 16.

Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Brazil. Electronic address:

Mammalian nuclear distribution genes encode proteins with essential roles in neuronal migration and brain formation during embryogenesis. The implication of human nuclear distribution genes, namely nudC and NDE1 (Nuclear Distribution Element 1) / NDEL1 (Nuclear Distribution Element-Like 1), in psychiatric disorders including schizophrenia and bipolar disorder, has been recently described. The partial loss of NDEL1 expression results in neuronal migration defects, while ndel1 null knockout (KO) leads to early embryonic lethality in mice. Read More

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The dinucleotide composition of the Zika virus genome is shaped by conflicting evolutionary pressures in mammalian hosts and mosquito vectors.

PLoS Biol 2021 Apr 19;19(4):e3001201. Epub 2021 Apr 19.

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Read More

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Acinar cell NLRP3 inflammasome and GSDMD activation mediates pyroptosis and systemic inflammation in acute pancreatitis.

Br J Pharmacol 2021 Apr 19. Epub 2021 Apr 19.

Center of Severe Acute Pancreatitis (CASP), Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background And Purpose: Pyroptosis is a lytic form of proinflammatory cell death characterised as caspase-1-dependent with canonical NLRP3 inflammasome-induced gasdermin D (GSDMD) activation. We aimed to investigate the role of acinar pyroptotic cell death in pancreatic injury and systemic inflammation in acute pancreatitis (AP).

Experimental Approach: Pancreatic acinar pyroptotic cell death pathway activation upon pancreatic toxin stimulation in vitro and in vivo were investigated. Read More

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DCC regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation.

Elife 2021 Apr 19;10. Epub 2021 Apr 19.

Queensland Brain Institute, School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.

The forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). DCC and NTN1 are molecules that have an evolutionarily conserved function in commissural axon guidance. Read More

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