Search results for "Knockout"
showing 10 items of 806 documents
PGC-1α: a master gene that is hard to master
2012
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that favorably affects mitochondrial function. This concept is supported by an increasing amount of data including studies in PGC-1α gene-deleted mice, suggesting that PGC-1α is a rescue factor capable of boosting cell metabolism and promoting cell survival. However, this view has now been called into question by a recent study showing that adeno-associated virus-mediated PGC-1α overexpression causes overt cell degeneration in dopaminergic neurons. How is this to be understood, and can these seemingly conflicting findings tell us something about the role of PGC-1α in cell stress and in cont…
NADPH Oxidase Accounts for Enhanced Superoxide Production and Impaired Endothelium-Dependent Smooth Muscle Relaxation in BKβ1 −/− Mice
2006
Objective— Nitric oxide (NO)-induced vasorelaxation involves activation of large conductance Ca 2+ -activated K + channels (BK). A regulatory BKβ1 subunit confers Ca 2+ , voltage, and NO/cGMP sensitivity to the BK channel. We investigated whether endothelial function and NO/cGMP signaling is affected by a deletion of the β1-subunit. Methods and Results— Vascular superoxide in BKβ1 −/− was measured using the fluorescent dye hydroethidine and lucigenin-enhanced chemiluminescence. Vascular NO formation was analyzed using electron paramagnetic resonance (EPR), expression of NADPH oxidase subunits, the endothelial NO synthase (eNOS), the soluble guanylyl cyclase (sGC), as well as the activity a…
IRS-2 deficiency impairs NMDA receptor-dependent long-term potentiation
2011
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.-- et al.
Genetic Deletion of JNK1 and JNK2 Aggravates the DSS-Induced Colitis in Mice
2007
The c-Jun N-terminal kinases (JNKs) are considered as novel targets for therapy of inflammatory bowel diseases (IBD). However, the relevant JNK isoforms have to be elucidated. Here, we analyze the individual contribution of the JNK1 and JNK2 isoforms in a dextran sulfate sodium (DSS) model of experimental colitis. JNK1 and JNK2 knockout mice (JNK1 ko, JNK2 ko) and their wild-type controls (WT1, WT2) received three cycles of DSS treatment, each consisting of 1.7% DSS for 5 days, followed by 5 days with water. Animals were daily evaluated by a disease activity index (DAI) comprising measurement of body weight, estimation of stool consistency, and test for occult blood/gross rectal bleeding. A…
The identification of peroxisome proliferator-activated receptor alpha-independent effects of oleoylethanolamide on intestinal transit in mice
2009
Oleoylethanolamide (OEA) is an endogenous lipid produced in the intestine that mediates satiety by activation of peroxisome proliferator-activated receptor alpha (PPARalpha). OEA inhibits gastric emptying and intestinal motility, but the mechanism of action remains to be determined. We investigated whether OEA inhibits intestinal motility by activation of PPARalpha. PPARalpha immunoreactivity was examined in whole mount preparations of mouse gastrointestinal (GI) tract. The effect of OEA on motility was assessed in wildtype, PPARalpha, cannabinoid CB(1) receptor and CB(2) receptor gene-deficient mice and in a model of accelerated GI transit. In addition, the effect of OEA on motility was as…
Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction
2013
Endocannabinoids are important regulators of organ homeostasis. Although their role in systemic vasculature has been extensively studied, their impact on pulmonary vessels remains less clear. Herein, we show that the endocannabinoid anandamide (AEA) is a key mediator of hypoxic pulmonary vasoconstriction (HPV) via fatty acid amide hydrolase (FAAH)-dependent metabolites. This is underscored by the prominent vasoconstrictive effect of AEA on pulmonary arteries and strongly reduced HPV in FAAH(-/-) mice and wild-type mice upon pharmacological treatment with FAAH inhibitor URB597. In addition, mass spectrometry measurements revealed a clear increase of AEA and the FAAH-dependent metabolite arac…
Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: A link to autonomic dysfunction in Parkinson's disease
2010
Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein…
Agouti-related peptide-expressing neurons are mandatory for feeding.
2005
Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.
Nitric oxide triggers mammary gland involution after weaning: remodelling is delayed but not impaired in mice lacking inducible nitric oxide synthase
2010
During mammary gland involution, different signals are required for apoptosis and tissue remodelling. To explore the role of NO in the involution of mammary tissue after lactation, NOS2 (inducible nitric oxide synthase)-KO (knockout) mice were used. No apparent differences were observed between NOS2-KO and WT (wild-type) animals during pregnancy and lactation. However, upon cessation of lactation, a notable delay in involution was observed, compared with WT mice. NOS2-KO mice showed increased phosphorylation of STAT (signal transducer and activator of transcription) 5 during weaning, concomitant with increased beta-casein mRNA levels when compared with weaned WT glands, both hallmarks of th…
BDNF is essentially required for the early postnatal survival of nociceptors
2010
AbstractNeurotrophins promote the survival of specific types of neurons during development and ensure proper maintenance and function of mature responsive neurons. Significant effects of BDNF (Brain-Derived Neurotrophic Factor) on pain physiology have been reported but the contribution of this neurotrophin to the development of nociceptors has not been investigated. We present evidence that BDNF is required for the survival of a significant fraction of peptidergic and non-peptidergic nociceptors in dorsal root ganglia (DRG) postnatally. Bdnf homozygous mutant mice lose approximately half of all nociceptive neurons during the first 2 weeks of life and adult heterozygotes exhibit hypoalgesia …