6,243 results match your criteria knockout allele


Mouse LGR6 regulates osteogenesis in vitro and in vivo through differential ligand use.

Bone 2021 Nov 29:116267. Epub 2021 Nov 29.

Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address:

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a marker of osteoprogenitor cells and is dynamically expressed during in vitro osteodifferentation of mouse and human mesenchymal stem cells (MSCs). While the Lgr6 genomic locus has been associated with osteoporosis in human cohorts, the precise molecular function of LGR6 in osteogenesis and maintenance of bone mass are not yet known. In this study, we performed in vitro Lgr6 knockdown and overexpression experiments in murine osteoblastic cells and find decreased Lgr6 levels results in reduced osteoblast proliferation, differentiation, and mineralization. Read More

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November 2021

Involvement of the Clock Gene in the Photoperiodism of the Silkmoth .

Zoolog Sci 2021 Dec;38(6):523-530

Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan,

We established a knockout strain of a clock gene, (), by using TALEN in a bivoltine strain (Kosetsu) of (Insecta, Lepidoptera), and examined the effect of knockout on the circadian rhythm and photoperiodism. The generated knockout allele was considered to be null, because a new stop codon was present in the insertion allele. The wild type (Kosetsu) showed clear circadian rhythms in eclosion and hatching, whereas the knockout strain showed arrhythmic eclosion and hatching under constant darkness. Read More

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December 2021

An efficient i-GONAD method for creating and maintaining lethal mutant mice using an inversion balancer identified from the C3H/HeJJcl strain.

G3 (Bethesda) 2021 Aug;11(8)

Center for Education in Laboratory Animal Research, Chubu University, Kasugai, Aichi 487-8501, Japan.

As the efficiency of the clustered regularly interspaced short palindromic repeats/Cas system is extremely high, creation and maintenance of homozygous lethal mutants are often difficult. Here, we present an efficient in vivo electroporation method called improved genome editing via oviductal nucleic acid delivery (i-GONAD), wherein one of two alleles in the lethal gene was selectively edited in the presence of a non-targeted B6.C3H-In(6)1J inversion identified from the C3H/HeJJcl strain. Read More

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Pulmonary Alveolar Stem Cell Senescence, Apoptosis, and Differentiation by p53-Dependent and -Independent Mechanisms in Telomerase-Deficient Mice.

Cells 2021 Oct 26;10(11). Epub 2021 Oct 26.

Institute of Ageing Research, Hangzhou Normal University School of Basic Medical Sciences, Hangzhou 311121, China.

Pulmonary premature ageing and fibrogenesis as in idiopathic pulmonary fibrosis (IPF) occur with the DNA damage response in lungs deficient of telomerase. The molecular mechanism mediating pulmonary alveolar cell fates remains to be investigated. The present study shows that naturally occurring ageing is associated with the DNA damage response (DDR) and activation of the p53 signalling pathway. Read More

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October 2021

Distinct Morphological and Behavioural Alterations in ENU-Induced Heterozygous Mutant Mice.

Genes (Basel) 2021 Oct 29;12(11). Epub 2021 Oct 29.

Chair for Molecular Animal Breeding and Biotechnology, Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany.

(transient receptor potential cation channel, subfamily C, member 7; 862 amino acids) knockout mice are described showing no clear phenotypic alterations, therefore, the functional relevance of the gene remains unclear. A complementary approach for the functional analysis of a given gene is the examination of individuals harbouring a mutant allele of the gene. In the phenotype-driven Munich ENU mouse mutagenesis project, a high number of phenotypic parameters was used for establishing novel mouse models on the genetic background of C3H inbred mice. Read More

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October 2021

Genetic Modifiers of Oral Nicotine Consumption in Null Mutant Mice.

Front Psychiatry 2021 4;12:773400. Epub 2021 Nov 4.

Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, United States.

The gene is strongly associated with the level of nicotine consumption in humans and manipulation of the expression or function of similarly alters nicotine consumption in rodents. In both humans and rodents, reduced or complete loss of function of leads to increased nicotine consumption. However, the mechanism through which decreased function of increases nicotine intake is not well-understood. Read More

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November 2021

Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice.

Front Neurosci 2021 5;15:728905. Epub 2021 Nov 5.

Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, Columbia University, New York, NY, United States.

The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21 day after birth as a result of renal underdevelopment. To extend the observation period, we generated the conditional knockout mouse model and analyzed the retinal function and morphological changes in mature and aging mice. Read More

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November 2021

Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia.

Am J Hum Genet 2021 Nov 17. Epub 2021 Nov 17.

Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran.

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. Read More

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November 2021

Kdm6a deficiency restricted to mouse hematopoietic cells causes an age- and sex-dependent myelodysplastic syndrome-like phenotype.

PLoS One 2021 15;16(11):e0255706. Epub 2021 Nov 15.

Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, United States of America.

Kdm6a/Utx, a gene on the X chromosome, encodes a histone H3K27me3 demethylase that has an orthologue on the Y chromosome (Uty) (Zheng et al. 2018). We previously identified inactivating mutations of Kdm6a in approximately 50% of mouse acute promyelocytic leukemia samples; however, somatic mutations of KDM6A are more rare in human AML samples, ranging in frequency from 2-15% in different series of patients, where their role in pathogenesis is not yet clear. Read More

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November 2021

The Functional Association of with Salt Stress Resistance in Was Confirmed by CRISPR-Mediated Mutagenesis.

Int J Mol Sci 2021 Oct 21;22(21). Epub 2021 Oct 21.

Center for Genome Engineering, Institute for Basic Science, Daejeon 34126, Korea.

Clustered regularly interspaced palindromic repeat (CRISPR)-mediated mutagenesis has become an important tool in plant research, enabling the characterization of genes via gene knock-out. CRISPR genome editing tools can be applied to generate multi-gene knockout lines. Typically, multiple single-stranded, single guide RNAs (gRNAs) must be expressed in an organism to target multiple genes simultaneously; however, a single gRNA can target multiple genes if the target genes share similar sequences. Read More

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October 2021

The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.

J Immunol 2021 12 5;207(11):2710-2719. Epub 2021 Nov 5.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA;

The single-nucleotide polymorphism (SNP) rs3184504 is broadly associated with increased risk for multiple autoimmune and cardiovascular diseases. Although the allele is uniquely enriched in European descent, the mechanism for the widespread selective sweep is not clear. In this study, we find the rs3184504*T allele had a strong association with reduced mortality in a human sepsis cohort. Read More

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December 2021

Semaphorin-Plexin Signaling: From Axonal Guidance to a New X-Linked Intellectual Disability Syndrome.

Pediatr Neurol 2021 Oct 18;126:65-73. Epub 2021 Oct 18.

Division of Neurology, Department of Pediatrics, Connecticut Children's, University of Connecticut, Farmington, Connecticut. Electronic address:

Background: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. Read More

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October 2021

Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone.

J Am Heart Assoc 2021 Nov 3;10(22):e022975. Epub 2021 Nov 3.

Division of Endocrinology, Diabetes, and Hypertension Department of Medicine Brigham and Women's Hospital Boston MA.

Background In addition to its role on blood pressure, aldosterone (ALDO) also affects the hemostatic system leading to increased experimental thrombosis. Striatin is an intermediate in the rapid, nongenomic actions of ALDO. Striatin heterozygote knockout () mice have salt sensitivity of blood pressure and mildly chronically increased ALDO levels. Read More

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November 2021

Immunocompromised Cas9 transgenic mice for rapid assessment of host factors involved in highly pathogenic virus infection.

Mol Ther Methods Clin Dev 2021 Dec 1;23:286-295. Epub 2021 Oct 1.

Department of Biotechnology and Bioengineering, Sandia National Laboratories, Livermore, CA 94550, USA.

Targeting host factors for anti-viral development offers several potential advantages over traditional countermeasures that include broad-spectrum activity and prevention of resistance. Characterization of host factors in animal models provides strong evidence of their involvement in disease pathogenesis, but the feasibility of performing high-throughput analyses on lists of genes is problematic. To begin addressing the challenges of screening candidate host factors , we combined advances in CRISPR-Cas9 genome editing with an immunocompromised mouse model used to study highly pathogenic viruses. Read More

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December 2021

Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome.

J Carcinog 2021 7;20:18. Epub 2021 Oct 7.

Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA.

Background: The tumor suppressor gene is the most commonly mutated gene in human cancers. Humans who inherit mutant alleles develop a wide range of early onset cancers, a disorder called Li-Fraumeni Syndrome (LFS). -deficient mice recapitulate most but not all of the cancer phenotypes observed in -deficient human cancers, indicating that new animal models may complement current mouse models and better inform on human disease development. Read More

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October 2021

Inactivating transcription factor OsWRKY5 enhances drought tolerance through abscisic acid signaling pathways.

Plant Physiol 2021 Oct 27. Epub 2021 Oct 27.

Department of Agriculture, Forestry and Bioresources, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.

During crop cultivation, water-deficit conditions retard growth, thus reducing crop productivity. Therefore, uncovering the mechanisms behind drought tolerance is a critical task for crop improvement. Here, we show that the rice (Oryza sativa) WRKY transcription factor OsWRKY5 negatively regulates drought tolerance. Read More

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October 2021

Combined fluorescent seed selection and multiplex CRISPR/Cas9 assembly for fast generation of multiple Arabidopsis mutants.

Plant Methods 2021 Oct 30;17(1):111. Epub 2021 Oct 30.

Department of Plant Molecular Biology, University of Lausanne, 1015, Lausanne, Switzerland.

Background: Multiplex CRISPR-Cas9-based genome editing is an efficient method for targeted disruption of gene function in plants. Use of CRISPR-Cas9 has increased rapidly in recent years and is becoming a routine method for generating single and higher order Arabidopsis thaliana mutants. Low entry, reliable assembly of CRISPR/Cas9 vectors and efficient mutagenesis is necessary to enable a maximum of researchers to break through the genetic redundancy within plant multi-gene families and allow for a plethora of gene function studies that have been previously unachievable. Read More

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October 2021

Progress towards completing the mutant mouse null resource.

Mamm Genome 2021 Oct 26. Epub 2021 Oct 26.

The Jackson Laboratory, Bar Harbor, ME, USA.

The generation of a comprehensive catalog of null alleles covering all protein-coding genes is the goal of the International Mouse Phenotyping Consortium. Over the past 20 years, significant progress has been made towards achieving this goal through the combined efforts of many large-scale programs that built an embryonic stem cell resource to generate knockout mice and more recently employed CRISPR/Cas9-based mutagenesis to delete critical regions predicted to result in frameshift mutations, thus, ablating gene function. The IMPC initiative builds on prior and ongoing work by individual research groups creating gene knockouts in the mouse. Read More

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October 2021

Dark-adapted light response in mice is regulated by a circadian clock located in rod photoreceptors.

Exp Eye Res 2021 Oct 23;213:108807. Epub 2021 Oct 23.

Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67084, Strasbourg, France. Electronic address:

The retinal circadian system consists of a network of clocks located virtually in every retinal cell-type. Although it is established that the circadian clock regulates many rhythmic processes in the retina, the links between retinal cell-specific clocks and visual function remain to be elucidated. Bmal1 is a principal, non-redundant component of the circadian clock in mammals and is required to keep 24 h rhythms in the retinal transcriptome and in visual processing under photopic light condition. Read More

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October 2021

Cardiac Investigations in Sudden Unexpected Death in DEPDC5-Related Epilepsy.

Ann Neurol 2021 Oct 24. Epub 2021 Oct 24.

Sorbonne University, Paris Brain Institute (ICM), Inserm, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.

Objective: Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP.

Methods: Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Read More

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October 2021

Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies.

Nat Commun 2021 10 18;12(1):6072. Epub 2021 Oct 18.

Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Primary congenital glaucoma (PCG) is a severe disease characterized by developmental defects in the trabecular meshwork (TM) and Schlemm's canal (SC), comprising the conventional aqueous humor outflow pathway of the eye. Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies. Read More

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October 2021

The dihydropyrimidine dehydrogenase gene contributes to heritable differences in sleep in mice.

Curr Biol 2021 Oct 8. Epub 2021 Oct 8.

Division of Sleep Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address:

Many aspects of sleep are heritable, but only a few sleep-regulating genes have been reported. Here, we leverage mouse models to identify and confirm a previously unreported gene affecting sleep duration-dihydropyrimidine dehydrogenase (Dpyd). Using activity patterns to quantify sleep in 325 Diversity Outbred (DO) mice-a population with high genetic and phenotypic heterogeneity-a linkage peak for total sleep in the active lights off period was identified on chromosome 3 (LOD score = 7. Read More

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October 2021

A genetic mouse model with postnatal and loss recapitulates the histology and transcriptome of human malignant peripheral nerve sheath tumor.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab129. Epub 2021 Sep 10.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of and cooperating tumor suppressors, including , PRC2, and p53, is found in most MPNST. Inactivation of LATS1/2 of the Hippo pathway was recently shown to cause tumors resembling MPNST histologically, although Hippo pathway mutations are rarely found in MPNST. Read More

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September 2021

SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.

Am J Hum Genet 2021 11 8;108(11):2112-2129. Epub 2021 Oct 8.

Institute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.

Upregulated signal flow through RAS and the mitogen-associated protein kinase (MAPK) cascade is the unifying mechanistic theme of the RASopathies, a family of disorders affecting development and growth. Pathogenic variants in more than 20 genes have been causally linked to RASopathies, the majority having a dominant role in promoting enhanced signaling. Here, we report that SPRED2 loss of function is causally linked to a recessive phenotype evocative of Noonan syndrome. Read More

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November 2021

Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer's disease.

Sci Rep 2021 Oct 8;11(1):20075. Epub 2021 Oct 8.

Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and behavioral changes. Extracellular deposition of amyloid plaques (Aβ) and intracellular deposition of neurofibrillary tangles in neurons are the major pathogenicities of AD. However, drugs targeting these therapeutic targets are not effective. Read More

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October 2021

Cloning and functional analysis of the novel rice blast resistance gene Pi65 in japonica rice.

Theor Appl Genet 2021 Oct 4. Epub 2021 Oct 4.

Rice Research Institute of Shenyang Agricultural University, Shenyang, 110866, China.

Key Message: Pi65, a leucine-rich repeat receptor-like kinase (LRR-RLK) domain cloned from Oryza sativa japonica, is a novel rice blast disease resistance gene. Rice blast seriously threatens rice production worldwide. Utilizing the rice blast resistance gene to breed rice blast-resistant varieties is one of the best ways to control rice blast disease. Read More

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October 2021

The PD1 inhibitory pathway and mature dendritic cells contribute to abacavir hypersensitivity in human leukocyte antigen transgenic PD1 knockout mice.

Toxicology 2021 Nov 1;463:152971. Epub 2021 Oct 1.

Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. Electronic address:

Based on recent genome-wide association studies, abacavir-induced hypersensitivity is highly associated with human leukocyte antigen (HLA)-B*57:01 allele. However, the underlying mechanism of this occurrence is unclear. To investigate the underlying mechanism, we developed HLA-B*57:01 transgenic mice and found that application of abacavir could cause CD8 T cell activation with elevation in PD1 expression; however, severe skin hypersensitivity was not observed. Read More

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November 2021

B-Cell RANKL Contributes to Pathogen-Induced Alveolar Bone Loss in an Experimental Periodontitis Mouse Model.

Front Physiol 2021 14;12:722859. Epub 2021 Sep 14.

Department of Oral Biology, University at Buffalo, Buffalo, NY, United States.

Periodontitis is a bacterially-induced inflammatory disease that leads to tooth loss. It results from the damaging effects of a dysregulated immune response, mediated largely by neutrophils, macrophages, T cells and B cells, on the tooth-supporting tissues including the alveolar bone. Specifically, infiltrating B cells at inflamed gingival sites with an ability to secrete RANKL and inflammatory cytokines are thought to play roles in alveolar bone resorption. Read More

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September 2021

Sex-dependent role of CD300f immune receptor in generalized anxiety disorder.

Brain Behav Immun Health 2021 Feb 14;11:100191. Epub 2020 Dec 14.

Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate not only in the modulation of immune responses but also in pruning and reshaping synapses. Read More

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February 2021

Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome.

PLoS Genet 2021 09 29;17(9):e1009777. Epub 2021 Sep 29.

Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMC, Illkirch, France.

Perturbation of the excitation/inhibition (E/I) balance leads to neurodevelopmental diseases including to autism spectrum disorders, intellectual disability, and epilepsy. Loss-of-function mutations in the DYRK1A gene, located on human chromosome 21 (Hsa21,) lead to an intellectual disability syndrome associated with microcephaly, epilepsy, and autistic troubles. Overexpression of DYRK1A, on the other hand, has been linked with learning and memory defects observed in people with Down syndrome (DS). Read More

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September 2021