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https://www.readbyqxmd.com/read/29463955/optic-nerve-regeneration-in-the-mouse-is-a-complex-trait-modulated-by-genetic-background
#1
Jiaxing Wang, Ying Li, Rebecca King, Felix L Struebing, Eldon E Geisert
Purpose: The present study is designed to identify the influences of genetic background on optic nerve regeneration using the two parental strains (C57BL/6J and DBA/2J) and seven BXD recombinant inbred mouse strains. Methods: To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using adenoassociated virus (AAV) delivery of shRNA, and a mild inflammatory response was induced with an intravitreal injection of zymosan with CPT-cAMP...
2018: Molecular Vision
https://www.readbyqxmd.com/read/28900002/modeling-parkinson-s-disease-pathology-by-combination-of-fibril-seeds-and-%C3%AE-synuclein-overexpression-in-the-rat-brain
#2
Poonam Thakur, Ludivine S Breger, Martin Lundblad, Oi Wan Wan, Bengt Mattsson, Kelvin C Luk, Virginia M Y Lee, John Q Trojanowski, Anders Björklund
Although a causative role of α-synuclein (α-syn) is well established in Parkinson's disease pathogenesis, available animal models of synucleinopathy do not replicate the full range of cellular and behavioral changes characteristic of the human disease. This study was designed to generate a more faithful model of Parkinson's disease by injecting human α-syn fibril seeds into the rat substantia nigra (SN), in combination with adenoassociated virus (AAV)-mediated overexpression of human α-syn, at levels that, by themselves, are unable to induce acute dopamine (DA) neurodegeneration...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28835534/local-gene-therapy-durably-restores-vestibular-function-in-a-mouse-model-of-usher-syndrome-type-1g
#3
Alice Emptoz, Vincent Michel, Andrea Lelli, Omar Akil, Jacques Boutet de Monvel, Ghizlene Lahlou, Anaïs Meyer, Typhaine Dupont, Sylvie Nouaille, Elody Ey, Filipa Franca de Barros, Mathieu Beraneck, Didier Dulon, Jean-Pierre Hardelin, Lawrence Lustig, Paul Avan, Christine Petit, Saaid Safieddine
Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27881908/functional-study-of-two-biochemically-unusual-mutations-in-gucy2d-leber-congenital-amaurosis-expressed-via-adenoassociated-virus-vector-in-mouse-retinas
#4
Sanford L Boye, Elena V Olshevskaya, Igor V Peshenko, K Tyler McCullough, Shannon E Boye, Alexander M Dizhoor
PURPOSE: To test, in living photoreceptors, two mutations, S248W and R1091x, in the GUCY2D gene linked to Leber congenital amaurosis 1 (LCA1) that fail to inactivate the catalytic activity of a heterologously expressed retinal membrane guanylyl cyclase 1 (RetGC1). METHODS: GUC2YD cDNA constructs coding for wild-type human (hWT), R1091x, and S248W GUCY2D under the control of the human rhodopsin kinase promoter were expressed in Gucy2e-/- Gucy2f-/- knockout (GCdKO) mouse retinas, which lack endogenous RetGC activity...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27587945/bcl-2-bcl-xl-and-p-akt-are-involved-in-neuroprotective-effects-of-transcription-factor-brn3b-in-an-ocular-hypertension-rat-model-of-glaucoma
#5
Nitasha R Phatak, Dorota L Stankowska, Raghu R Krishnamoorthy
PURPOSE: Brn3b is a class IV POU domain transcription factor that plays an important role in the development of retinal ganglion cells (RGCs), RGC survival, and particularly axon growth and pathfinding. Our previous study demonstrated that recombinant adenoassociated virus serotype 2 (rAAV-2)-mediated overexpression of Brn3b in RGCs promoted neuroprotection in a rodent model of glaucoma. However, the mechanisms underlying neuroprotection of RGCs in rats overexpressing Brn3b in animal models of glaucoma remain largely unknown...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27190495/a-therapeutic-role-for-survivin-in-mitigating-the-harmful-effects-of-ionizing-radiation
#6
Katherine H Carruthers, Gregory Metzger, Eugene Choi, Matthew J During, Ergun Kocak
Background. Radiation therapy is a form of adjuvant care used in many oncological treatment protocols. However, nonmalignant neighboring tissues are harmed as a result of this treatment. Therefore, the goal of this study was to induce the production of survivin, an antiapoptotic protein, to determine if this protein could provide protection to noncancerous cells during radiation exposure. Methods. Using a murine model, a recombinant adenoassociated virus (rAAV) was used to deliver survivin to the treatment group and yellow fluorescence protein (YFP) to the control group...
2016: Sarcoma
https://www.readbyqxmd.com/read/27178803/adeno-associated-virus-overexpression-of-angiotensin-converting-enzyme-2-reverses-diabetic-retinopathy-in-type-1-diabetes-in-mice
#7
James M Dominguez, Ping Hu, Sergio Caballero, Leni Moldovan, Amrisha Verma, Gavin Y Oudit, Qiuhong Li, Maria B Grant
Angiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections...
June 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26160631/heme-oxygenase-1-gene-therapy-provides-cardioprotection-via-control-of-post-ischemic-inflammation-an-experimental-study-in-a-pre-clinical-pig-model
#8
Rabea Hinkel, Philipp Lange, Björn Petersen, Elena Gottlieb, Judy King Man Ng, Stefanie Finger, Jan Horstkotte, Seungmin Lee, Michael Thormann, Maike Knorr, Chiraz El-Aouni, Peter Boekstegers, Bruno Reichart, Philip Wenzel, Heiner Niemann, Christian Kupatt
BACKGROUND: Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear. OBJECTIVES: This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model...
July 14, 2015: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/25820246/cystic-fibrosis-a-look-into-the-future-of-prenatal-screening-and-therapy
#9
REVIEW
Kevin Nishida, Zachary Smith, Dane Rana, Jereme Palmer, G Ian Gallicano
Despite recent guidelines suggesting prenatal screening for carriers of cystic fibrosis (CF) mutations, many physicians do not offer patients this service or even counseling. Some argue that the risks of miscarriage associated with prenatal diagnostic techniques outweigh the benefit of added insight, but with the advent of newer, noninvasive techniques, risks of miscarriage may be significantly lowered. Prenatal diagnosis provides parents the time to prepare for raising a child with CF, and soon, could provide treatment options in utero that could improve quality of life...
March 2015: Birth Defects Research. Part C, Embryo Today: Reviews
https://www.readbyqxmd.com/read/25633175/corrigendum-to-a-novel-chimeric-adenoassociated-virus-2-human-bocavirus-1-parvovirus-vector-efficiently-transduces-human-airway-epithelia
#10
(no author information available yet)
No abstract text is available yet for this article.
February 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/25592337/adenoassociated-virus-serotype-9-mediated-gene-therapy-for-x-linked-adrenoleukodystrophy
#11
Yi Gong, Dakai Mu, Shilpa Prabhakar, Ann Moser, Patricia Musolino, JiaQian Ren, Xandra O Breakefield, Casey A Maguire, Florian S Eichler
X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1) responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. We used recombinant adenoassociated virus serotype 9 (rAAV9) vector for delivery of the human ABCD1 gene (ABCD1) to mouse central nervous system (CNS). In vitro, efficient delivery of ABCD1 gene was achieved in primary mixed brain glial cells from Abcd1-/- mice as well as X-ALD patient fibroblasts...
May 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/25586688/intra-amniotic-raav-mediated-microdystrophin-gene-transfer-improves-canine-x-linked-muscular-dystrophy-and-may-induce-immune-tolerance
#12
Hiromi Hayashita-Kinoh, Naoko Yugeta, Hironori Okada, Yuko Nitahara-Kasahara, Tomoko Chiyo, Takashi Okada, Shin'ichi Takeda
Duchenne muscular dystrophy (DMD) is a severe congenital disease due to mutations in the dystrophin gene. Supplementation of dystrophin using recombinant adenoassociated virus vector has promise as a treatment of DMD, although therapeutic benefit of the truncated dystrophin still remains to be elucidated. Besides, host immune responses against the vector as well as transgene products have been denoted in the clinical gene therapy studies. Here, we transduced dystrophic dogs fetuses to investigate the therapeutic effects of an AAV vector expressing microdystrophin under conditions of immune tolerance...
April 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/25519733/brain-ace2-overexpression-reduces-doca-salt-hypertension-independently-of-endoplasmic-reticulum-stress
#13
Huijing Xia, Thyago Moreira de Queiroz, Srinivas Sriramula, Yumei Feng, Tanya Johnson, Imran N Mungrue, Eric Lazartigues
Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension...
March 1, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/25512545/stat3-promotes-survival-of-mutant-photoreceptors-in-inherited-photoreceptor-degeneration-models
#14
Ke Jiang, Katherine L Wright, Ping Zhu, Michael J Szego, Alexa N Bramall, William W Hauswirth, Qiuhong Li, Sean E Egan, Roderick R McInnes
Inherited photoreceptor degenerations (IPDs), a group of incurable progressive blinding diseases, are caused by mutations in more than 200 genes, but little is known about the molecular pathogenesis of photoreceptor (PR) death. Increased retinal expression of STAT3 has been observed in response to many retinal insults, including IPDs, but the role of this increase in PR death is unknown. Here, we show that the expression of Stat3 is increased in PRs of the Tg(RHO P347S) and Prph2(rds) (/+) mouse models of IPD and is activated by tyrosine phosphorylation...
December 30, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25476605/parallel-pathways-from-motor-and-somatosensory-cortex-for-controlling-whisker-movements-in-mice
#15
Varun Sreenivasan, Kajari Karmakar, Filippo M Rijli, Carl C H Petersen
Mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers...
February 2015: European Journal of Neuroscience
https://www.readbyqxmd.com/read/25457558/recombinant-adenoassociated-virus-2-5-mediated-gene-transfer-is-reduced-in-the-aged-rat-midbrain
#16
Nicole K Polinski, Sara E Gombash, Fredric P Manfredsson, Jack W Lipton, Christopher J Kemp, Allyson Cole-Strauss, Nicholas M Kanaan, Kathy Steece-Collier, Nathan C Kuhn, Susan L Wohlgenant, Caryl E Sortwell
Clinical trials are examining the efficacy of viral vector-mediated gene delivery for treating Parkinson's disease. Although viral vector strategies have been successful in preclinical studies, to date clinical trials have disappointed. This may be because of the fact that preclinical studies fail to account for aging. Aging is the single greatest risk factor for developing Parkinson's disease and age alters cellular processes utilized by viral vectors. We hypothesized that the aged brain would be relatively resistant to transduction when compared with the young adult...
February 2015: Neurobiology of Aging
https://www.readbyqxmd.com/read/25133251/highly-effective-ex-vivo-gene-manipulation-to-study-kidney-development-using-self-complementary-adenoassociated-viruses
#17
Tie-Lin Chen, Hong-Lian Wang, Yun-Hong Liu, Yin Fang, Rui-Zhi Tan, Pu-Hui Zhou, Qin Zhou, Xiao-Yan Lv
BACKGROUND: Ex vivo culture of intact embryonic kidney has become a powerful system for studying renal development. However, few methods have been available for gene manipulation and have impeded the identification and investigation of genes in this developmental process. RESULTS: Here we systemically compared eight different serotypes of pseudotyped self-complementary adenoassociated viruses (scAAVs) transduction in cultured embryonic kidney with a modified culture procedure...
2014: TheScientificWorldJournal
https://www.readbyqxmd.com/read/25114098/epigenetic-modification-at-notch-responsive-promoters-blunts-efficacy-of-inducing-notch-pathway-reactivation-after-myocardial-infarction
#18
Giulia Felician, Chiara Collesi, Marina Lusic, Valentina Martinelli, Matteo Dal Ferro, Lorena Zentilin, Serena Zacchigna, Mauro Giacca
RATIONALE: The Notch pathway plays a key role in stimulating mammalian cardiomyocyte proliferation during development and in the early postnatal life; in adult zebrafish, reactivation of this pathway is also essential to drive cardiac regeneration after injury. OBJECTIVE: We wanted to assess efficacy of Notch pathway stimulation in neonatal and adult hearts as a means to induce cardiac regeneration after myocardial infarction in mice. METHODS AND RESULTS: In early postnatal life, cardiomyocyte exit from the cell cycle was paralleled by decreased Notch signaling and the establishment of a repressive chromatin environment at Notch-responsive genes, characterized by recruitment of the polycomb group enhancer of zeste homolog 2 methyltransferase and the acquisition of the histone 3 Lysine 27 trimethylation histone mark, as detected by chromatin immunoprecipitation...
September 12, 2014: Circulation Research
https://www.readbyqxmd.com/read/24958505/increased-expression-of-angiotensin-ii-type-2-receptors-in-the-solitary-vagal-complex-blunts-renovascular-hypertension
#19
Graziela Torres Blanch, André Henrique Freiria-Oliveira, Guilherme Fleury Fina Speretta, Eduardo J Carrera, Hongwei Li, Robert C Speth, Eduardo Colombari, Colin Sumners, Débora S A Colombari
Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors, respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin-angiotensin system. Therefore, in the present study, we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus), a key brain stem region for cardiovascular regulation, on the development of renovascular hypertension...
October 2014: Hypertension
https://www.readbyqxmd.com/read/24876262/postacute-stromal-cell-derived-factor-1%C3%AE-expression-promotes-neurovascular-recovery-in-ischemic-mice
#20
Yaning Li, Jun Huang, Xiaosong He, Guanghui Tang, Yao-Hui Tang, Yanqun Liu, Xiaojie Lin, Yifan Lu, Guo-Yuan Yang, Yongting Wang
BACKGROUND AND PURPOSE: Acute interventions of stroke are often challenged by a narrow treatment window. In this study, we explore treatments in the postacute phase of stroke with wider windows of opportunity. We investigated the effects of stromal cell-derived factor (SDF-1α) in neurovascular recovery during the postacute phase and downstream signaling pathways, underlying SDF-1α-mediated neurovascular recovery. METHODS: Adult male Institute of Cancer Research (ICR) mice underwent middle cerebral artery occlusion...
June 2014: Stroke; a Journal of Cerebral Circulation
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