97,662 results match your criteria mutant mice

Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models.

NPJ Vaccines 2021 Apr 19;6(1):61. Epub 2021 Apr 19.

Sanofi Pasteur, Marcy l'Etoile, France.

Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches. Read More

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Aim2 and Nlrp3 Are Dispensable For Vaccine-Induced Immunity Against Live Vaccine Strain.

Infect Immun 2021 Apr 19. Epub 2021 Apr 19.

Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USA

() is a facultative intracellular, Gram-negative bacterium that causes a fatal disease known as tularemia. Due to its extremely high virulence, ease of spread by aerosolization, and the potential to be used as a bioterror agent, is classified by the CDC as a Tier 1 Category A Select Agent. Previous studies have demonstrated the roles of inflammasome sensors; absent in melanoma 2 (AIM2) and NLRP3, in the generation of innate immune responses to infection. 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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K3.1 channels regulate the rate of critical period plasticity.

Neurosci Res 2021 Apr 16. Epub 2021 Apr 16.

Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan; International Research Center for Neuorintelligence, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113, Japan; Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA, 02138, USA. Electronic address:

Experience-dependent plasticity within visual cortex is controlled by postnatal maturation of inhibitory circuits, which are both morphologically diverse and precisely connected. Gene-targeted disruption of the voltage-dependent potassium channel K3.1 broadens action potentials and reduces net inhibitory function of parvalbumin (PV)-positive GABA subtypes within the neocortex. 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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MACF1, Involved in the 1p34.2p34.3 Microdeletion Syndrome, is Essential in Cortical Progenitor Polarity and Brain Integrity.

Cell Mol Neurobiol 2021 Apr 19. Epub 2021 Apr 19.

Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA.

1p34.2p34.3 deletion syndrome is characterized by an increased risk for autism. Read More

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Downregulation of glial genes involved in synaptic function mitigates Huntington's Disease pathogenesis.

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

Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.

Most research on neurodegenerative diseases has focused on neurons, yet glia help form and maintain the synapses whose loss is so prominent in these conditions. To investigate the contributions of glia to Huntington's disease (HD), we profiled the gene expression alterations of expressing human mutant (m) in either glia or neurons and compared these changes to what is observed in HD human and HD mice striata. A large portion of conserved genes are concordantly dysregulated across the three species; we tested these genes in a high-throughput behavioral assay and found that downregulation of genes involved in synapse assembly mitigated pathogenesis and behavioral deficits. Read More

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MEKK1 Regulates Chemokine Expression in Mammary Fibroblasts: Implications for the Breast Tumor Microenvironment.

Front Oncol 2021 18;11:609918. Epub 2021 Mar 18.

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.

Breast tumors contain both transformed epithelial cells and non-transformed stroma cells producing secreted factors that can promote metastasis. Previously, we demonstrated that the kinase MEKK1 regulates cell migration and gene expression, and that transgene-induced breast tumor metastasis is markedly inhibited in MEKK1-deficient mice. In this report, we examined the role of MEKK1 in stroma cell gene expression and the consequent effect on breast tumor cell function. Read More

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Wild-type IDH1 inhibits the tumor growth through degrading HIF-α in renal cell carcinoma.

Int J Biol Sci 2021 25;17(5):1250-1262. Epub 2021 Mar 25.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

The purpose of our study was to explore the effect and intrinsic mechanism of wild-type IDH1 and its substrate α-KG on renal cell carcinoma (RCC). IDH1 was observed lower expression in RCC cell lines. Phenotype experiment was carried out in the wild-type IDH1 and mutant IDH1 plasmid treated cell line. Read More

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Precision modeling of gall bladder cancer patients in mice based on orthotopic implantation of organoid-derived tumor buds.

Oncogenesis 2021 Apr 17;10(4):33. Epub 2021 Apr 17.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, 236-0004, Japan.

Genetically engineered mice (GEM) are the gold standard for cancer modeling. However, strict recapitulation of stepwise carcinogenesis from a single tumor-initiating epithelial cell among genetically intact cells in adults is not feasible with the currently available techniques using GEM. In previous studies, we partially overcame this challenge by physically isolating organs from adult animals, followed by genetic engineering in organoids and subcutaneous inoculation in nude mice. Read More

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The transcriptional regulator GON4L is required for viability and hematopoiesis in mice.

Exp Hematol 2021 Apr 14. Epub 2021 Apr 14.

Departments of Internal MedicineCarver College of Medicine, University of Iowa, 375 Newton Road, Iowa City, IA, 52242, USA; Anatomy and Cell BiologyCarver College of Medicine, University of Iowa, 375 Newton Road, Iowa City, IA, 52242, USA; Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, 375 Newton Road, Iowa City, IA, 52242, USA. Electronic address:

The Gon4l gene encodes a putative transcriptional regulator implicated in the control of both cell differentiation and proliferation. Previously, we described a mutant mouse strain called Justy in which splicing of pre-mRNA generated from Gon4l is disrupted. This defect severely reduces, but does not abolish, GON4L protein expression, and blocks the formation of early B-lineage progenitors, suggesting Gon4l is required for B cell development in vertebrates. Read More

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Modeling muscle Regeneration in RNA toxicity mice.

Hum Mol Genet 2021 Apr 16. Epub 2021 Apr 16.

Department of Pathology, University of Virginia, Charlottesville, VA, 22908, USA.

RNA toxicity underlies the pathogenesis of disorders such as myotonic dystrophy (DM1). Muscular dystrophy is a key element of the pathology of DM1. The means by which RNA toxicity causes muscular dystrophy in DM1 is unclear. Read More

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Myeloperoxidase Targets Apolipoprotein A-I for Site-Specific Tyrosine Chlorination in Atherosclerotic Lesions and Generates Dysfunctional High-Density Lipoprotein.

Chem Res Toxicol 2021 Apr 16. Epub 2021 Apr 16.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Jiangxi Key Laboratory of Green Chemistry, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear. Read More

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Deficiency in Nebulin Repeats of Sarcomeric Nebulette is Detrimental for Cardiomyocyte Tolerance to Exercise and Biomechanical Stress.

Am J Physiol Heart Circ Physiol 2021 Apr 16. Epub 2021 Apr 16.

The Heart Institute, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; Children's Foundation Research Institute, Le Bonheur Children's Hospital Memphis, TN, United States.

Background: The actin-binding sarcomeric nebulette (NEBL) protein provides efficient contractile flexibility via interaction with desmin intermediate filaments. NEBL gene mutations affecting the nebulin repeat (NR) domain is known to induce cardiomyopathy.

Objective: The study aimed to explore the roles of NEBL in exercise and biomechanical stress response. Read More

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Inhalation delivery dramatically improves the efficacy of topotecan for the treatment of local and distant lung cancer.

Drug Deliv 2021 Dec;28(1):767-775

Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.

Topotecan is potent anti-cancer drug approved for various malignancies but hematopoietic toxicities undermine its wider application and use of its most effective dose. This study aims to improve these limitations through inhalation-delivery. The pharmacokinetics, efficacy, and toxicity of 2-5 times lower inhalation doses of topotecan dry-powder were compared with the standard intravenous (IV) delivery once/twice-a-week. Read More

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December 2021

Intracerebroventricular Administration of AAV9-PHP.B SYN1-EmGFP Induces Widespread Transgene Expression in the Mouse and Monkey CNS.

Hum Gene Ther 2021 Apr 16. Epub 2021 Apr 16.

Emory University, 1371, Yerkes National Primate Research Center, Atlanta, Georgia, United States.

Viral vectors made from adeno-associated virus (AAV) have emerged as preferred tools in basic and translational neuroscience research to introduce or modify genetic material in cells of interest. The use of viral vectors is particularly attractive in non-transgenic species, such as non-human primates. Injections of AAV solutions into the cerebrospinal fluid (CSF) is an effective method to achieve a broad distribution of a transgene in the central nervous system. Read More

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A novel tissue specific alternative splicing variant mitigates phenotypes in Ets2 frame-shift mutant models.

Sci Rep 2021 Apr 15;11(1):8297. Epub 2021 Apr 15.

Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara, 630-0192, Japan.

E26 avian leukemia oncogene 2, 3' domain (Ets2) has been implicated in various biological processes. An Ets2 mutant model (Ets2), which lacks the DNA-binding domain, was previously reported to exhibit embryonic lethality caused by a trophoblast abnormality. This phenotype could be rescued by tetraploid complementation, resulting in pups with wavy hair and curly whiskers. Read More

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Mirogabalin activates the descending noradrenergic system by binding to the αδ-1 subunit of voltage-gated Ca channels to generate analgesic effects.

J Pharmacol Sci 2021 May 7;146(1):33-39. Epub 2021 Jan 7.

Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address:

Gabapentinoids such as gabapentin and pregabalin, which bind specifically to the αδ subunit of voltage-gated Ca channels, are used for first-line treatment of neuropathic pain. Here, we examined the analgesic effect of mirogabalin besilate (referred to simply as mirogabalin), a novel gabapentinoid, focusing on its action on the spinal cord and the descending noradrenergic pain inhibitory system. When administered systemically (10 and 30 mg/kg, intraperitoneally (i. Read More

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Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/- Mice.

Radiat Res 2021 Apr 15. Epub 2021 Apr 15.

Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.

Experimental mouse studies are important to gain a comprehensive, quantitative and mechanistic understanding of the biological factors that modify individual risk of radiation-induced health effects, including age at exposure, dose, dose rate, organ/tissue specificity and genetic factors. In this study, neonatal Ptch1+/- mice bred on CD1 and C57Bl/6 background received whole-body irradiation at postnatal day 2. This time point represents a critical phase in the development of the eye lens, cerebellum and dentate gyrus (DG), when they are also particularly susceptible to radiation effects. Read More

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Bone phenotype of P2X4 receptor knockout mice: implication of a P2X7 receptor mutation?

Purinergic Signal 2021 Apr 15. Epub 2021 Apr 15.

Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.

Transgenic and knockout animal models are widely used to investigate the role of receptors, signaling pathways, and other peptides and proteins. Varying results are often published on the same model from different groups, and much effort has been put into understanding the underlying causes of these sometimes conflicting results. Recently, it has been shown that a P2X4R knockout model carries a so-called passenger mutation in the P2X7R gene, potentially affecting the interpretation of results from studies using this animal model. Read More

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Proteomic analysis of aged and OPTN E50K retina in the development of normal tension glaucoma.

Hum Mol Genet 2021 Apr 15. Epub 2021 Apr 15.

Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Progressive degeneration of retinal ganglion cells (RGCs) is a major characteristic of glaucoma, whose underlying mechanisms are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal tension glaucoma (NTG), directly affecting RGCs without high intraocular pressure and causing severe glaucomatous symptoms in clinical settings. A systematic analysis of the NTG mouse model is crucial for better understanding of the underlying pathological mechanisms for glaucoma. Read More

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Mint3 depletion-mediated glycolytic and oxidative alterations promote pyroptosis and prevent the spread of Listeria monocytogenes infection in macrophages.

Cell Death Dis 2021 Apr 14;12(4):404. Epub 2021 Apr 14.

Division of Cellular and Molecular Biology, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.

Listeria monocytogenes (LM) infection induces pyroptosis, a form of regulated necrosis, in host macrophages via inflammasome activation. Here, we examined the role of Mint3 in macrophages, which promotes glycolysis via hypoxia-inducible factor-1 activation, during the initiation of pyroptosis following LM infection. Our results showed that Mint3-deficient mice were more resistant to lethal listeriosis than wild-type (WT) mice. Read More

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Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington's disease.

Acta Neuropathol Commun 2021 04 14;9(1):70. Epub 2021 Apr 14.

Institute of Structural and Molecular Biology, Birkbeck College, London, WC1E 7HX, UK.

Huntington's disease (HD) is a late onset, inherited neurodegenerative disorder for which early pathogenic events remain poorly understood. Here we show that mutant exon 1 HTT proteins are recruited to a subset of cytoplasmic aggregates in the cell bodies of neurons in brain sections from presymptomatic HD, but not wild-type, mice. This occurred in a disease stage and polyglutamine-length dependent manner. Read More

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Osteoblast lineage cells and periodontal ligament fibroblasts regulate orthodontic tooth movement that is dependent on Nuclear Factor-kappa B (NF-kB) activation.

Angle Orthod 2021 Apr 14. Epub 2021 Apr 14.

Objectives: To investigate the role of NF-κB in osteoblast lineage cells and periodontal ligament (PDL) fibroblasts during orthodontic tooth movement (OTM).

Materials And Methods: Transgenic mice that expressed a dominant negative mutant of the inhibitor of kB kinase (IKK-DN) with lineage specific expression in osteoblastic cells and PDL fibroblasts driven by a response element in the collagen1α1 promoter and matched wild-type (WT) mice were examined. A 10-12 g force was applied by a NiTi coil and maintained for 5 or 12 days. Read More

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Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions.

iScience 2021 Apr 8;24(4):102283. Epub 2021 Mar 8.

Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University, Hanns-Dieter-Hüsch-Weg 17, 55099 Mainz, Germany.

VLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion G protein-coupled receptor in humans. Homozygous pathologic variants of cause hereditary deaf blindness in Usher syndrome 2C and haploinsufficiency of is associated with epilepsy. However, its molecular function remains elusive. Read More

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Bacterial Microcompartments Coupled with Extracellular Electron Transfer Drive the Anaerobic Utilization of Ethanolamine in Listeria monocytogenes.

mSystems 2021 Apr 13;6(2). Epub 2021 Apr 13.

Food Microbiology, Wageningen University and Research, Wageningen, the Netherlands

Ethanolamine (EA) is a valuable microbial carbon and nitrogen source derived from cell membranes. EA catabolism is suggested to occur in a cellular metabolic subsystem called a bacterial microcompartment (BMC), and the activation of EA utilization () genes is linked to bacterial pathogenesis. Despite reports showing that the activation of is regulated by a vitamin B-binding riboswitch and that upregulation of genes occurs in mice, it remains unknown whether EA catabolism is BMC dependent in Here, we provide evidence for BMC-dependent anaerobic EA utilization via metabolic analysis, proteomics, and electron microscopy. Read More

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Septal chondrocyte hypertrophy contributes to midface deformity in a mouse model of Apert syndrome.

Sci Rep 2021 Apr 12;11(1):7979. Epub 2021 Apr 12.

Department of Molecular Genetics and Dental Pharmacology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.

Midface hypoplasia is a major manifestation of Apert syndrome. However, the tissue component responsible for midface hypoplasia has not been elucidated. We studied mice with a chondrocyte-specific Fgfr2 mutation (Col2a1-cre; Fgfr2) to investigate the effect of cartilaginous components in midface hypoplasia of Apert syndrome. Read More

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Functional cooperation between ASK1 and p21 in the balance of cell-cycle arrest, cell death and tumorigenesis of stressed keratinocytes.

Cell Death Discov 2021 Apr 12;7(1):75. Epub 2021 Apr 12.

Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, Rome, 00161, Italy.

Both CDKN1A (p21 ) and Apoptosis signal-regulating kinase 1 (ASK1) play important roles in tumorigenesis. The role of p21 in attenuating ASK1-induced apoptosis by various stress conditions is well established. However, how ASK1 and p21 functionally interact during tumorigenesis is still unclear. Read More

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In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers.

Genome Med 2021 Apr 12;13(1):57. Epub 2021 Apr 12.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

Background: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD.

Methods: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. Read More

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Two novel mouse models mimicking minor deletions in 22q11.2 deletion syndrome revealed the contribution of each deleted region to psychiatric disorders.

Mol Brain 2021 Apr 12;14(1):68. Epub 2021 Apr 12.

Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by the segmental deletion of human chromosome 22. Read More

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