8,186 results match your criteria conditional knockout

Estrogen Receptor-α Suppresses Liver Carcinogenesis and Establishes Sex-Specific Gene Expression.

Cancers (Basel) 2021 May 13;13(10). Epub 2021 May 13.

McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA.

Estrogen protects females from hepatocellular carcinoma (HCC). To determine whether this protection is mediated by classic estrogen receptors, we tested HCC susceptibility in estrogen receptor-deficient mice. In contrast to a previous study, we found that diethylnitrosamine induces hepatocarcinogenesis to a significantly greater extent when females lack , which encodes Estrogen Receptor-α. Read More

View Article and Full-Text PDF

Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice.

Int J Mol Sci 2021 May 12;22(10). Epub 2021 May 12.

Department of Cellular Biology and Anatomy, LSUHSC-Shreveport, Shreveport, LA 71130, USA.

Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. Read More

View Article and Full-Text PDF

Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function.

Int J Mol Sci 2021 May 11;22(10). Epub 2021 May 11.

Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.

To characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as ), a central exocyst component. We analyzed both zebrafish mutants and retinal pigmented epithelium (RPE)-specific knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. Read More

View Article and Full-Text PDF

Ablation of Lrp4 in Schwann Cells Promotes Peripheral Nerve Regeneration in Mice.

Biology (Basel) 2021 May 21;10(6). Epub 2021 May 21.

School of Life Sciences, Nanchang University, Nanchang 330031, China.

Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Read More

View Article and Full-Text PDF

A20 functions as a negative regulator in macrophage for DSS-induced colitis.

Int Immunopharmacol 2021 May 29;97:107804. Epub 2021 May 29.

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan, China. Electronic address:

The function of A20 as a deubiquitinating enzyme in inflammatory diseases and autoimmune diseases has been reported, we therefore aimed to investigate the potential effects of A20 in macrophages and dextran sodium sulfate (DSS)-induced colitis mouse model. Colitis mouse model was induced by DSS treatment. Tnfaip3 mice were crossed with Lyz2-Cre mice to generate A20 myeloid cell-conditional knockout mice. Read More

View Article and Full-Text PDF

Hedgehog signalling controls sinoatrial node development and atrioventricular cushion formation.

Open Biol 2021 Jun 2;11(6):210020. Epub 2021 Jun 2.

Henan Key Laboratory for Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan Province, People's Republic of China.

Smoothened is a key receptor of the hedgehog pathway, but the roles of Smoothened in cardiac development remain incompletely understood. In this study, we found that the conditional knockout of from the mesoderm impaired the development of the venous pole of the heart and resulted in hypoplasia of the atrium/inflow tract (IFT) and a low heart rate. The blockage of led to reduced expression of genes critical for sinoatrial node (SAN) development in the IFT. Read More

View Article and Full-Text PDF

Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice.

Nat Commun 2021 05 31;12(1):3321. Epub 2021 May 31.

State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P. R. China.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. Read More

View Article and Full-Text PDF

Inactivation of the Schizophrenia-associated BRD1 gene in Brain Causes Failure-to-thrive, Seizure Susceptibility and Abnormal Histone H3 Acetylation and N-tail Clipping.

Mol Neurobiol 2021 May 31. Epub 2021 May 31.

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.

Genetic studies have repeatedly shown that the Bromodomain containing 1 gene, BRD1, is involved in determining mental health, and the importance of the BRD1 protein for normal brain function has been studied in both cell models and constitutive haploinsufficient Brd1 mice. Homozygosity for inactivated Brd1 alleles is lethal during embryonic development in mice. In order to further characterize the molecular functions of BRD1 in the brain, we have developed a novel Brd1 knockout mouse model (Brd1) with bi-allelic conditional inactivation of Brd1 in the central nervous system. Read More

View Article and Full-Text PDF

Deficiency Causes Germ Cell Loss During Mouse Embryogenesis and Is Associated With Human Male Infertility.

Front Cell Dev Biol 2021 13;9:658966. Epub 2021 May 13.

Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling germ cell development. The RNA-binding protein and E3 ubiquitin ligase TRIM71 is essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional knockout mouse (cKO) using the early primordial germ cell (PGC) marker as a Cre-recombinase driver. Read More

View Article and Full-Text PDF

A critical role for Th17 cell-derived TGF-β1 in regulating the stability and pathogenicity of autoimmune Th17 cells.

Exp Mol Med 2021 May 28;53(5):993-1004. Epub 2021 May 28.

Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.

Pathogenic conversion of Th17 cells into multifunctional helper T cells or Th1 cells contributes to the pathogenesis of autoimmune diseases; however, the mechanism regulating the plasticity of Th17 cells remains unclear. Here, we found that Th17 cells expressed latent TGF-β1 in a manner dependent on autocrine TGF-β1. By employing IL-17-producing cell-specific Tgfb1 conditional knockout and fate-mapping systems, we demonstrated that TGF-β1-deficient Th17 cells are relatively susceptible to becoming IFN-γ producers through IL-12Rβ2 and IL-27Rα upregulation. Read More

View Article and Full-Text PDF

Neocortex- and hippocampus-specific deletion of Gabrg2 causes temperature-dependent seizures in mice.

Cell Death Dis 2021 May 28;12(6):553. Epub 2021 May 28.

Ningxia Key Laboratory of Cerebrocranial Disease, The Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia, China.

Mutations in the GABRG2 gene encoding the γ-aminobutyric acid (GABA) A receptor gamma 2 subunit are associated with genetic epilepsy with febrile seizures plus, febrile seizures plus, febrile seizures, and other symptoms of epilepsy. However, the mechanisms underlying Gabrg2-mediated febrile seizures are poorly understood. Here, we used the Cre/loxP system to generate conditional knockout (CKO) mice with deficient Gabrg2 in the hippocampus and neocortex. Read More

View Article and Full-Text PDF

Digging behavior discrimination test to probe burrowing and exploratory digging in male and female mice.

J Neurosci Res 2021 May 28. Epub 2021 May 28.

Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Child Health Institute of New Jersey, New Brunswick, NJ, USA.

Digging behavior is often used to test motor function and repetitive behaviors in mice. Different digging paradigms have been developed for behaviors related to anxiety and compulsion in mouse lines generated to recapitulate genetic mutations leading to psychiatric and neurological disorders. However, the interpretation of these tests has been confounded by the difficulty of determining the motivation behind digging in mice. Read More

View Article and Full-Text PDF

GPR37 is processed in the N-terminal ectodomain by ADAM10 and furin.

FASEB J 2021 Jun;35(6):e21654

Medical Research Center Oulu, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.

GPR37 is an orphan G protein-coupled receptor (GPCR) implicated in several neurological diseases and important physiological pathways in the brain. We previously reported that its long N-terminal ectodomain undergoes constitutive metalloprotease-mediated cleavage and shedding, which have been rarely described for class A GPCRs. Here, we demonstrate that the protease that cleaves GPR37 at Glu167↓Gln168 is a disintegrin and metalloprotease 10 (ADAM10). Read More

View Article and Full-Text PDF

Characterization of the direct pathway in Dyt1 ΔGAG heterozygous knock-in mice and dopamine receptor 1-expressing-cell-specific Dyt1 conditional knockout mice.

Behav Brain Res 2021 May 24;411:113381. Epub 2021 May 24.

Norman Fixel Institute for Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, 32610-0236, USA. Electronic address:

DYT1 dystonia is a movement disorder mainly caused by a trinucleotide deletion (ΔGAG) in DYT1 (TOR1A), coding for torsinA. DYT1 dystonia patients show trends of decreased striatal ligand-binding activities to dopamine receptors 1 (D1R) and 2 (D2R). Dyt1 ΔGAG knock-in (KI) mice, which have the corresponding ΔGAG deletion, similarly exhibit reduced striatal D1R and D2R-binding activities and their expression levels. Read More

View Article and Full-Text PDF

NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development.

Nucleic Acids Res 2021 06;49(10):5760-5778

School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.

Alternative pre-mRNA splicing is a critical step to generate multiple transcripts, thereby dramatically enlarging the proteomic diversity. Thus, a common feature of most alternative splicing factor knockout models is lethality. However, little is known about lineage-specific alternative splicing regulators in a physiological setting. Read More

View Article and Full-Text PDF

Inactivation of Presenilin in inhibitory neurons results in decreased GABAergic responses and enhanced synaptic plasticity.

Mol Brain 2021 May 25;14(1):85. Epub 2021 May 25.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease (AD). Presenilin (PS) is highly expressed in the hippocampus, which is particularly vulnerable in AD. Previous studies of PS function in the hippocampus, however, focused exclusively on excitatory neurons. Read More

View Article and Full-Text PDF

MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus.

Development 2021 May 25;148(10). Epub 2021 May 25.

Department of Experimental Biology, Faculty of Science, Masaryk University, Brno 61137, Czech Republic.

The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. Read More

View Article and Full-Text PDF

The KDM4B-CCAR1-MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis.

Bone Res 2021 May 25;9(1):27. Epub 2021 May 25.

Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Recent studies have shown that histone demethylases are implicated in osteoblastogenesis; however, little is known about the role of histone demethylases in osteoclast formation. Here, we identified KDM4B as an epigenetic regulator of osteoclast differentiation. Read More

View Article and Full-Text PDF

The essential roles of Mps1 in spermatogenesis and fertility in mice.

Cell Death Dis 2021 May 24;12(6):531. Epub 2021 May 24.

Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

Monopolar spindle 1 (MPS1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of MPS1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. Read More

View Article and Full-Text PDF

The CNOT4 Subunit of the CCR4-NOT Complex is Involved in mRNA Degradation, Efficient DNA Damage Repair, and XY Chromosome Crossover during Male Germ Cell Meiosis.

Adv Sci (Weinh) 2021 05 16;8(10):2003636. Epub 2021 Mar 16.

MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University Hangzhou 310058 China.

The CCR4-NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6/6L and CNOT7/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. knockout male mice have been reported to be infertile. Read More

View Article and Full-Text PDF

Cldn-7 deficiency promotes experimental colitis and associated carcinogenesis by regulating intestinal epithelial integrity.

Oncoimmunology 2021 May 11;10(1):1923910. Epub 2021 May 11.

Department of Oncology Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Intestinal epithelial barrier protects intestine from infection and injury, while chronic inflammation is a trigger for tumorigenesis. As a member of tight junctions (TJs) family, Claudin-7 (Cldn-7) is dedicated to maintaining cell polarity and TJs barrier integrity, and closely related to the development of inflammation and tumors. However, potential roles of Cldn-7 in intestinal inflammation and colitis-associated colorectal cancer (CAC) have not been well characterized in vivo. Read More

View Article and Full-Text PDF

Cdc42 has important roles in postnatal angiogenesis and vasculature formation.

Dev Biol 2021 May 18;477:64-69. Epub 2021 May 18.

Department of Perioperative Medicine, Division of Anesthesiology, School of Dentistry, Showa University, Tokyo, Japan.

Cdc42, a Rho family low molecular weight G protein, has important roles in various cell functions, including cytoskeletal rearrangement, cell adhesion and cell proliferation and differentiation. To investigate the involvement of Cdc42 in the activities of vascular endothelial cells, we generated Cdc42 conditional knockout mice in which Cdc42 was time -specifically deficient in vascular endothelial cells (Cdc42 ​; VE-Cad CreERT: Cdc42 cKO). When the Cdc42 gene was deleted after birth, Cdc42 cKO mice were smaller than the control mice, and died between postnatal day 8 (P8) and P10. Read More

View Article and Full-Text PDF

Homeobox Gene Six3 is Required for the Differentiation of D2-Type Medium Spiny Neurons.

Neurosci Bull 2021 May 20. Epub 2021 May 20.

Institute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.

Medium spiny neurons (MSNs) in the striatum, which can be divided into D1 and D2 MSNs, originate from the lateral ganglionic eminence (LGE). Previously, we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs. Here, we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature. Read More

View Article and Full-Text PDF

Microglial MERTK eliminates phosphatidylserine-displaying inhibitory post-synapses.

EMBO J 2021 May 19:e107121. Epub 2021 May 19.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.

Glia contribute to synapse elimination through phagocytosis in the central nervous system. Despite the important roles of this process in development and neurological disorders, the identity and regulation of the "eat-me" signal that initiates glia-mediated phagocytosis of synapses has remained incompletely understood. Here, we generated conditional knockout mice with neuronal-specific deletion of the flippase chaperone Cdc50a, to induce stable exposure of phosphatidylserine, a well-known "eat-me" signal for apoptotic cells, on the neuronal outer membrane. Read More

View Article and Full-Text PDF

Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental animal model of sepsis.

Blood 2021 May 19. Epub 2021 May 19.

Changhai Hospital, the Second Military Medical University, Shanghai, China.

PD-L1 is a ligand for PD-1 and its expression has been shown to be upregulated in neutrophils harvested from septic patients. However, the effect of PD-L1 on neutrophil survival and sepsis-induced lung injury remains largely unknown. Here we show PD-L1 expression negatively correlates with rates of apoptosis in human neutrophils harvested from patients with sepsis. Read More

View Article and Full-Text PDF

Loss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning, and causes an autism-like phenotype.

EMBO J 2021 Jun 19;40(12):e107471. Epub 2021 May 19.

Department of Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.

The key role of APP for Alzheimer pathogenesis is well established. However, perinatal lethality of germline knockout mice lacking the entire APP family has so far precluded the analysis of its physiological functions for the developing and adult brain. Here, we generated conditional APP/APLP1/APLP2 triple KO (cTKO) mice lacking the APP family in excitatory forebrain neurons from embryonic day 11. Read More

View Article and Full-Text PDF

Mapping Rora expression in resting and activated CD4+ T cells.

PLoS One 2021 18;16(5):e0251233. Epub 2021 May 18.

EMBL-European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.

The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. Read More

View Article and Full-Text PDF

Regulation of murine B lymphopoiesis by stromal cells.

Immunol Rev 2021 May 17. Epub 2021 May 17.

Stem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Vic., Australia.

B lymphocytes are crucial for the body's humoral immune response, secreting antibodies generated against foreign antigens to fight infection. Adult murine B lymphopoiesis is initiated in the bone marrow and additional maturation occurs in the spleen. In both these organs, B lymphopoiesis involves interactions with numerous different non-hematopoietic cells, also known as stromal or microenvironment cells, which provide migratory, maturation, and survival signals. Read More

View Article and Full-Text PDF

Hyperprolactinemia in a male pituitary androgen receptor knockout mouse is associated with female-like lactotroph development.

Andrology 2021 May 16. Epub 2021 May 16.

MRC Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, UK.

Background: Circulating prolactin concentration in rodents and humans is sexually dimorphic. Oestrogens are a well-characterised stimulator of prolactin release. Circulating prolactin fluctuates throughout the menstrual/oestrous cycle of females in response to oestrogen levels, but remains continually low in males. Read More

View Article and Full-Text PDF

NF-κB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells.

Front Immunol 2021 29;12:652786. Epub 2021 Apr 29.

Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, United States.

Natural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-κB c-Rel results in a marked decrease in cytotoxic function of NK cells, both and , with no significant differences in the stages of NK cell development. We found that c-Rel binds to the promoters of perforin and granzyme B, two key proteins required for NK cytotoxicity, and controls their expression. Read More

View Article and Full-Text PDF