120,322 results match your criteria wild-type mice

Indoleamine-2,3-Dioxygenase Activates Wnt/β-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury.

Gerontology 2021 Jun 15:1-9. Epub 2021 Jun 15.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Introduction: As disorder of tryptophan metabolism is common in CKD, the rate-limiting enzyme of tryptophan, indoleamine-2,3-dioxygenase (IDO), has been reported to be involved in CKD, while the accurate mechanism remains unknown. This study was designed to explore correlations between IDO and kidney fibrosis after ischemia-reperfusion injury (IRI).

Methods: Wild-type (WT) mice and IDO knockout (IDO-/-) mice were divided into the sham group and acute kidney injury (AKI) group. Read More

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UCP1 expression in the mouse adrenal gland is not upregulated by thermogenic conditions.

Biochem Biophys Res Commun 2021 Jun 12;566:184-189. Epub 2021 Jun 12.

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan. Electronic address:

The uncoupling protein 1 (UCP1) gene is known to be highly expressed in brown adipose tissue (BAT) that functions in thermogenesis. It has been shown that UCP1 mRNA is localized to the mouse adrenal gland, but its significance remains elusive. To explore how UCP1 expression in the adrenal gland is regulated, we generated a reporter knock-in mouse in which the GFP gene was inserted into the UCP1 locus using CRISPR-Cas9 system. Read More

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Na,K-ATPase α4, and Not Na,K-ATPase α1, is the Main Contributor to Sperm Motility, But its High Ouabain Binding Affinity Site is Not Required for Male Fertility in Mice.

J Membr Biol 2021 Jun 15. Epub 2021 Jun 15.

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas, KS, 66160, USA.

Mammalian sperm express two Na,K-ATPase (NKA) isoforms, Na,K-ATPase α4 (NKAα4) and Na,K-ATPase α1 (NKAα1). While NKAα4 is critical to sperm motility, the role of NKAα1 in sperm movement remains unknown. We determined this here using a genetic and pharmacological approach, modifying the affinity of NKAα1 and NKAα4 for the inhibitor ouabain to selectively block the function of each isoform. Read More

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Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake.

J Gen Physiol 2021 Aug 15;153(8). Epub 2021 Jun 15.

Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA.

Extracellular solutes in the central nervous system are exchanged between the interstitial fluid, the perivascular compartment, and the cerebrospinal fluid (CSF). The "glymphatic" mechanism proposes that the astrocyte water channel aquaporin-4 (AQP4) is a major determinant of solute transport between the CSF and the interstitial space; however, this is controversial in part because of wide variance in experimental data on interstitial uptake of cisternally injected solutes. Here, we investigated the determinants of solute uptake in brain parenchyma following cisternal injection and reexamined the role of AQP4 using a novel constant-pressure method. Read More

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Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression.

bioRxiv 2021 Jun 7. Epub 2021 Jun 7.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Read More

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In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer's disease.

Sci Rep 2021 Jun 14;11(1):12419. Epub 2021 Jun 14.

BRAIN Centre (Biomarker Research and Imaging for Neuroscience), Department of Neuroimaging, King's College London, The James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK.

Amyloid plaques are a hallmark of Alzheimer's disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Read More

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Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis.

Sci Rep 2021 Jun 14;11(1):12432. Epub 2021 Jun 14.

School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.

Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. Read More

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Gasdermin D in peripheral nerves: the pyroptotic microenvironment inhibits nerve regeneration.

Cell Death Discov 2021 Jun 14;7(1):144. Epub 2021 Jun 14.

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Wallerian degeneration (WD) involves the recruitment of macrophages for debris clearance and nerve regeneration, and the cause of the foamy macrophages that are frequently observed in peripheral transection injuries is unknown. Recent studies indicated that these foamy cells are generated by gasdermin D (GSDMD) via membrane perforation. However, whether these foamy cells are pyroptotic macrophages and whether their cell death elicits immunogenicity in peripheral nerve regeneration (PNR) remain unknown. Read More

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Macula Densa NOS1β Modulates Renal Hemodynamics and Blood Pressure During Pregnancy: Role in Gestational Hypertension.

J Am Soc Nephrol 2021 Jun 14. Epub 2021 Jun 14.

R Liu, Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, United States

Regulation of renal hemodynamics and blood pressure (BP) via tubuloglomerular feedback (TGF) may be an important adaptive mechanism during pregnancy. Because the β-splice variant of nitric oxide synthase 1 (NOS1β) in the macula densa is a primary modulator of TGF, we evaluated its role in normal pregnancy and gestational hypertension in a mouse model. We hypothesized that pregnancy upregulates NOS1β in the macula densa, thus blunting TGF, allowing glomerular filtration rate (GFR) to increase and BP to decrease. Read More

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Involvement of Activation of Mast Cells via IgE Signaling and Epithelial Cell-Derived Cytokines in the Pathogenesis of Pollen Food Allergy Syndrome in a Murine Model.

J Immunol 2021 Jun 14. Epub 2021 Jun 14.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Fukui, Fukui, Japan.

Murine models to elucidate the pathogenesis of pollen food allergy syndrome (PFAS), characterized by oral hypersensitivity symptoms induced by specific foods in patients previously sensitized with a pollen, are lacking. The study aimed to examine PFAS pathogenesis in a novel murine model. Birch pollen-immunized mice were orally administered apple extract, and oral symptoms were evaluated based on oral rubbing frequency following the challenge. Read More

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Toll-like Receptor 2 (TLR2) Deficiency Abrogates Diabetic and Obese Phenotypes while Restoring Endothelial Function via Inhibition of NOX1.

Diabetes 2021 Jun 14. Epub 2021 Jun 14.

Division of Molecular Medicine, Department of Anesthesiology, Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095;

We have previously demonstrated a novel role of bone morphogenic protein-4 (BMP4) in inducing NOX1-dependent eNOS uncoupling, endothelial dysfunction, and inflammatory activation in type 2 diabetes mellitus (T2DM). However, it has remained unclear as to how BMP4 activates NOX1 and whether targeting the new mechanistic pathway revealed is effective in preserving endothelial function in T2DM. Here we observed that BMP4 induced marked, time-dependent increase in physiological binding between TLR2 and NOX1 in aortic endothelial cells, as well as increased binding of TLR2 to NOXO1. Read More

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Reversible GABAergic dysfunction involved in hippocampal hyperactivity predicts early-stage Alzheimer disease in a mouse model.

Alzheimers Res Ther 2021 Jun 14;13(1):114. Epub 2021 Jun 14.

Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, China.

Background: Neuronal hyperactivity related to β-amyloid (Aβ) is considered an early warning sign of Alzheimer disease (AD). Although increasing evidence supports this opinion, the underlying mechanisms are still unknown.

Methods: Here, we recorded whole-cell synaptic currents and membrane potentials using patch clamping of acute hippocampal slices from human amyloid precursor protein (APP)/presenilin-1 transgenic (5XFAD) mice and their wild-type littermates. Read More

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Optical Stimulation of Thalamic Spindle Circuitry Sustains Electroencephalogram Patterns of General Anesthesia but not Duration of Loss of Consciousness.

Neuroscience 2021 Jun 11. Epub 2021 Jun 11.

Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. Electronic address:

Alterations in thalamic GABAergic signaling are implicated in mediating the rise in 12-30Hz electroencephalogram (EEG) activity that signals anesthetic-induced loss-of-consciousness with GABA receptor-targeting general anesthetics. A number of modeling studies have identified that anesthetic-induced alterations in thalamocortico-corticothalamic signaling in the same network that generates sleep spindles would be sufficient to elicit this key EEG signature of anesthetic hypnosis with general anesthetic agents. Accordingly, we hypothesize that targeted stimulation of this thalamic GABAergic circuitry into a sleep-spindle mode of activity would promote the general anesthetic effects of etomidate. Read More

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Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome.

Neurosci Lett 2021 Jun 11:136048. Epub 2021 Jun 11.

Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA; Molecular, Cellular and Integrative Neurosciences Program, Colorado State University, Fort Collins, CO, 80523, USA. Electronic address:

Chromosome 4q21 microdeletion leads to a human syndrome that exhibits restricted growth, facial dysmorphisms, mental retardation, and absent or delayed speech. One of the key genes in the affected region of the chromosome is PRKG2, which encodes cGMP-dependent protein kinase II (cGKII). Mice lacking cGKII exhibit restricted growth and deficits in learning and memory, as seen in the human syndrome. Read More

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Bone marrow transplantation without myeloablative conditioning in a mouse model for Diamond-Blackfan Anemia corrects the disease phenotype.

Exp Hematol 2021 Jun 11. Epub 2021 Jun 11.

Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden. Electronic address:

Diamond-Blackfan Anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes coding for ribosomal proteins. Among these genes, the ribosomal protein S19 (RPS19) gene is the most frequently mutated. Previously, a mouse model deficient in RPS19 was developed by our laboratory, which recapitulates the hematopoietic disease phenotype by displaying pathological features and clinical symptoms of DBA. Read More

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Multiple lesions contribute to infertility in males lacking autoimmune regulator (AIRE).

Am J Pathol 2021 Jun 11. Epub 2021 Jun 11.

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI; Cell and Molecular Biology Graduate Program, College of Natural Sciences, Michigan State University, East Lansing, MI. Electronic address:

Male factors, including those of autoimmune origin, contribute to approximately 50% of infertility cases in humans. However, the mechanisms underlying autoimmune male infertility are poorly understood. Deficiency in autoimmune regulator (AIRE) impairs central immune tolerance because of diminished expression of self-antigens in the thymus. Read More

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Vitamin C deficiency inhibits non-alcoholic fatty liver disease progression through impaired de novo lipogenesis.

Am J Pathol 2021 Jun 11. Epub 2021 Jun 11.

Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Despite the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD), little is known about its underlying pathogenesis or specific treatment. The senescence marker protein 30 (SMP30), which regulates the biosynthesis of vitamin C in many mammals except primates and humans, was recently recognized as a gluconolactonase. However, the precise relation between vitamin C and lipid metabolism in NAFLD is not completely understood. Read More

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Contribution of M-opsin-based color vision to refractive development in mice.

Exp Eye Res 2021 Jun 11:108669. Epub 2021 Jun 11.

Department of Ophthalmology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital Affiliated to Fudan University, Shanghai, China. Electronic address:

M-opsin, encoded by opn1mw gene, is involved in green-light perception of mice. The role of M-opsin in emmetropization of mice remains uncertain. To answer the above question, 4-week-old wild-type (WT) mice were exposed to white light or green light (460-600 nm, a peak at 510 nm) for 12 weeks. Read More

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Study of the host specificity of PB1-F2-associated virulence.

Virulence 2021 Dec;12(1):1647-1660

Université Paris-Saclay, INRAE, UVSQ, UMR892 VIM, Jouy-en-Josas, France.

Influenza A viruses cause important diseases in both human and animal. The PB1-F2 protein is a virulence factor expressed by some influenza viruses. Its deleterious action for the infected host is mostly described in mammals, while the available information is scarce in avian hosts. Read More

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December 2021

A novel mouse AAV6 hACE2 transduction model of wild-type SARS-CoV-2 infection studied using synDNA immunogens.

iScience 2021 Jun 8:102699. Epub 2021 Jun 8.

Public Health Agency of Canada. Winnipeg, Manitoba, Canada.

More than 100 million people have been infected with SARS-CoV-2. Common laboratory mice are not susceptible to wild-type SARS-CoV-2 infection, challenging the development and testing of effective interventions. Here, we describe the development and testing of a mouse model for SARS-CoV-2 infection based on transduction of the respiratory tract of laboratory mice with an adeno-associated virus vector () expressing human ACE-2 (). Read More

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Interleukin-10 Attenuates Liver Fibrosis Exacerbated by Thermoneutrality.

Front Med (Lausanne) 2021 26;8:672658. Epub 2021 May 26.

Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine, Daejeon, South Korea.

Crosstalk between brown adipose tissue (BAT) and the liver is receiving increasing attention. This study investigated the effect of BAT dysfunction by thermoneutral (TN) housing on liver fibrosis in mice and examined the effect of secreted factors from brown adipocytes on the activation of hepatic stellate cells (HSCs). The carbon tetrachloride (CCl)-induced liver fibrosis mouse model was used to evaluate fibrotic changes in the livers of mice housed under standard and TN conditions. Read More

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Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells.

Oncoimmunology 2021 Jun 6;10(1):1932061. Epub 2021 Jun 6.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.

The vast majority (>90%) of glioblastoma (GBM) patients belong to the isocitrate dehydrogenase 1 wild type (IDH1) group which exhibits a poor prognosis with a median survival of less than 15 months. This study demonstrated numerous immunosuppressive genes as well as β-catenin gene, pivotal for Wnt/β-catenin signaling, were upregulated in 206 IDH1 glioma patients using the Chinese Glioma Genome Atlas (CGGA) database. The increase in microglia with an immunosuppressive phenotype and the overexpression of β-catenin protein were further verified in IDH1 GBM patients and IDH1 GL261 glioma allografts. Read More

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Sorafenib Modulates the LPS- and Aβ-Induced Neuroinflammatory Response in Cells, Wild-Type Mice, and 5xFAD Mice.

Front Immunol 2021 27;12:684344. Epub 2021 May 27.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu, South Korea.

Sorafenib is FDA-approved for the treatment of primary kidney or liver cancer, but its ability to inhibit many types of kinases suggests it may have potential for treating other diseases. Here, the effects of sorafenib on neuroinflammatory responses and and the underlying mechanisms were assessed. Sorafenib reduced the induction of mRNA levels of the proinflammatory cytokines COX-2 and IL-1β by LPS in BV2 microglial cells, but in primary astrocytes, only COX-2 mRNA levels were altered by sorafenib. Read More

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Dominant-Negative Effect of an Brugada Syndrome Variant.

Front Physiol 2021 28;12:661413. Epub 2021 May 28.

INSERM, UMR_S 1166 ICAN, Paris, France.

Loss-of-function mutations in the cardiac Na channel α-subunit Na1.5, encoded by , cause Brugada syndrome (BrS), a hereditary disease characterized by sudden cardiac death due to ventricular fibrillation. We previously evidenced the dominant-negative effect of the BrS Na1. Read More

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Selective Wnt/β-Catenin Pathway Activation Concomitant With Sustained Overexpression of miR-21 is Responsible for Aristolochic Acid-Induced AKI-to-CKD Transition.

Front Pharmacol 2021 28;12:667282. Epub 2021 May 28.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Acute kidney injury (AKI) is increasingly recognized as a cumulative risk factor for chronic kidney disease (CKD) progression. However, the underlying mechanisms remain unclear. Using an aristolochic acid (AA)-induced mouse model of AKI-to-CKD transition, we found that the development of tubulointerstitial fibrosis following AKI was accompanied with a strong activation of miR-21 and canonical Wnt signaling, whereas inhibition of miR-21 or selective silencing of Wnt ligands partially attenuated AKI-to-CKD transition. Read More

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Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures.

Front Cell Neurosci 2021 28;15:688905. Epub 2021 May 28.

Department of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.

Parvalbumin-expressing (PV+) interneurons are a subset of GABAergic inhibitory interneurons that mediate feed-forward inhibition (FFI) within the cortico-thalamocortical (CTC) network of the brain. The CTC network is a reciprocal loop with connections between cortex and thalamus. FFI PV+ interneurons control the firing of principal excitatory neurons within the CTC network and prevent runaway excitation. Read More

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The influence of intermittent hypoxia, obesity and diabetes on male genitourinary anatomy and voiding physiology.

Am J Physiol Renal Physiol 2021 06 14. Epub 2021 Jun 14.

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.

We used male BTBR mice carrying the Lep mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 weeks of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia, on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (NX, control) or intermittent hypoxia (IH) to wild type and Lep (mutant) mice for 2 weeks. Intermittent hypoxia was delivered during the 12-hour inactive (lighted) period in the form of 90 sec of 6% O2 followed by 90 sec of room air. Read More

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Dissection, in vivo imaging and analysis of the mouse epitrochleoanconeus muscle.

J Anat 2021 Jun 13. Epub 2021 Jun 13.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.

Analysis of rodent muscles affords an opportunity to glean key insights into neuromuscular development and the detrimental impact of disease-causing genetic mutations. Muscles of the distal leg, for instance the gastrocnemius and tibialis anterior, are commonly used in such studies with mice and rats. However, thin and flat muscles, which can be dissected, processed and imaged without major disruption to muscle fibres and nerve-muscle contacts, are more suitable for accurate and detailed analyses of the peripheral motor nervous system. Read More

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TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice.

J Alzheimers Dis 2021 Jun 8. Epub 2021 Jun 8.

Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.

Background: Genetic mutations in triggering receptor expressed on myeloid cells-2 (TREM2) have been strongly associated with increased risk of developing Alzheimer's disease (AD) and other progressive dementias. In the brain, TREM2 protein is specifically expressed on microglia suggesting their active involvement in driving disease pathology. Using various transgenic AD models to interfere with microglial function through TREM2, several recent studies provided important data indicating a causal link between TREM2 and underlying amyloid-β (Aβ) and tau pathology. Read More

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PirB functions as an intrinsic suppressor in hippocampal neural stem cells.

Aging (Albany NY) 2021 Jun 13;13. Epub 2021 Jun 13.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.

Neural stem cells play pivotal roles during prenatal development and throughout life. Here, we report that Paired immunoglobulin-like receptor B (PirB) functions as a suppressor during brain neurogenesis in the adult mouse. PirB expression increased with age during development, and its deficiency promoted neural stem cell proliferation and differentiation and . Read More

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