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https://www.readbyqxmd.com/read/28339687/extra-gonadal-oocytes-residing-in-the-mouse-ovarian-hilum-contribute-to-fertility1
#1
Xiaofei Sun, Junya Ito, Sarah J Potter, Sudhansu K Dey, Tony DeFalco
The observation of pups born from recipient and donor mice after ovariectomy followed by ovarian transplant poses the interesting possibility of an extra-ovarian source of oocytes. However, whether mammalian adult oocytes reside in extra-gonadal tissues remains elusive. Using transgenic fluorescent reporter mice and transplantation surgeries, we demonstrate the presence of both donor- and recipient-derived corpora lutea and recovery of both donor- and recipient-derived offspring from ovariectomized mice after transplantation of donor ovaries...
February 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339476/transgenic-mice-overexpressing-desmocollin-2-dsc2-develop-cardiomyopathy-associated-with-myocardial-inflammation-and-fibrotic-remodeling
#2
Andreas Brodehl, Darrell D Belke, Lauren Garnett, Kristina Martens, Nelly Abdelfatah, Marcela Rodriguez, Catherine Diao, Yong-Xiang Chen, Paul M K Gordon, Anders Nygren, Brenda Gerull
BACKGROUND: Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion of cardiomyocytes; however, the molecular and cellular mechanisms underlying the disease remain widely unknown. Desmocollin-2 is a desmosomal cadherin serving as an anchor molecule required to reconstitute homeostatic intercellular adhesion with desmoglein-2...
2017: PloS One
https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#3
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334913/tdp-43-mutations-causing-amyotrophic-lateral-sclerosis-are-associated-with-altered-expression-of-rna-binding-protein-hnrnp-k-and-affect-the-nrf2-antioxidant-pathway
#4
Diane Moujalled, Alexandra Grubman, Karla Acevedo, Shu Yang, Yazi D Ke, Donia M Moujalled, Clare Duncan, Aphrodite Caragounis, Nirma D Perera, Bradley J Turner, Mercedes Prudencio, Leonard Petrucelli, Ian Blair, Lars M Ittner, Peter J Crouch, Jeffrey R Liddell, Anthony R White
TAR DNA binding protein 43 (TDP-43) is a major disease-associated protein involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous studies found a direct association between TDP-43 and heterogeneous nuclear ribonucleoprotein K (hnRNP K). In this study, utilizing ALS patient fibroblasts harboring a TDP-43M337V mutation and NSC-34 motor neuronal cell line expressing TDP-43Q331K mutation, we show that hnRNP K expression is impaired in urea soluble extracts from mutant TDP-43 cell models...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333097/effects-of-a-sativex-like-combination-of-phytocannabinoids-on-disease-progression-in-r6-2-mice-an-experimental-model-of-huntington-s-disease
#5
Sara Valdeolivas, Onintza Sagredo, Mercedes Delgado, Miguel A Pozo, Javier Fernández-Ruiz
Several cannabinoids afforded neuroprotection in experimental models of Huntington's disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆⁸-tetrahydrocannabinol (∆⁸-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex(®), is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD. We recorded the progression of neurological deficits and the extent of striatal deterioration, using behavioral, in vivo imaging, and biochemical methods in R6/2 mice and their corresponding wild-type mice...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332231/development-of-humanized-mice-in-the-age-of-genome-editing
#6
Vishnu Hosur, Benjamin E Low, Cindy Avery, Leonard D Shultz, Michael V Wiles
Mice are the most commonly used model organisms to study human disease. Many genetic human diseases can be recapitulated by modifying the mouse genome, which permits testing of existing and novel therapeutics, including combinatorial therapeutics, without putting humans at risk. Specifically, the development of "humanized" mice, i.e., severely immunodeficient mice engrafted with functional human hematopoietic and immune cells and tissues, has revolutionized our ability to study and model human diseases in preclinical in vivo systems...
March 22, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28331190/natural-killer-cell-activation-contributes-to-hepatitis-b-viral-control-in-a-mouse-model
#7
Shiwen Tong, Guangze Liu, Minghong Li, Xiumei Li, Qian Liu, Hong Peng, Shiying Li, Hong Ren, Wenwei Yin
The roles of CD4 + T cells and CD8 + T cells in hepatitis B virus (HBV) infection have been well documented. However, the role of innate immunity in HBV infection remains obscure. Here we examined the effect of activation of innate immunity by polyinosinic: polycytidylic acid (PolyI:C) on HBV infection. A chronic HBV replication mouse model was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. We found that HBV did not seem to induce an active NK-cell response in the mouse model...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331061/an-intracellular-matrix-metalloproteinase-2-isoform-induces-tubular-regulated-necrosis-implications-for-acute-kidney-injury
#8
Carla S Ceron, Celine Baligand, Sunil K Joshi, Shaynah Wanga, Patrick M Cowley, Joy P Walker, Sang Heon Song, Rajeev Mahimkar, Anthony J Baker, Robert L Raffai, Zhen J Wang, David H Lovett
Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with pre-existing CKD. Oxidative stress is a common theme in models of AKI induced by ischemia/reperfusion (I/R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an N-terminal truncated MMP-2 isoform (NTT-MMP-2) that is intracellular and associated with mitochondria...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28330720/attenuation-of-uvr-induced-vitamin-d3-synthesis-in-a-mouse-model-deleted-for-keratinocyte-lathosterol-5-desaturase
#9
Anastasia M Makarova, Saloni Pasta, Gordon Watson, Cedric Shackleton, Ervin H Epstein
The lower risk of some internal cancers at lower latitudes has been linked to greater sun exposure and consequent higher levels of ultraviolet radiation (UVR)-produced vitamin D3 (D3). To separate the experimental effects of sunlight and of all forms of D3, a mouse in which UVR does not produce D3 would be useful. To this end we have generated mice carrying a modified allele of sterol C5-desaturase (Sc5d), the gene encoding the enzyme that converts lathosterol to 7-dehydrocholesterol (7-DHC), such that Sc5d expression can be inactivated using the Cre/lox site-specific recombination system...
March 19, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28330719/nicotinamide-mononucleotide-inhibits-jnk-activation-to-reverse-alzheimer-disease
#10
Zhiwen Yao, Wenhao Yang, Zhiqiang Gao, Peng Jia
Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice...
March 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28327181/soluble-oligomeric-amyloid-%C3%AE-induces-calcium-dyshomeostasis-that-precedes-synapse-loss-in-the-living-mouse-brain
#11
Michal Arbel-Ornath, Eloise Hudry, Josiah R Boivin, Tadafumi Hashimoto, Shuko Takeda, Kishore V Kuchibhotla, Steven Hou, Carli R Lattarulo, Arianna M Belcher, Naomi Shakerdge, Pariss B Trujillo, Alona Muzikansky, Rebecca A Betensky, Bradley T Hyman, Brian J Bacskai
BACKGROUND: Amyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer's disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological effects. Even though AD mouse models remain a valuable resource to investigate amyloid neurotoxicity, the concomitant presence of soluble Aβ species, fibrillar Aβ, and fragments of amyloid precursor protein (APP) complicate the interpretation of the phenotypes. METHOD: To explore the specific contribution of soluble oligomeric Aβ (oAβ) to calcium dyshomeostasis and synaptic morphological changes, we acutely exposed the healthy mouse brain, at 3 to 6 months of age, to naturally occurring soluble oligomers and investigated their effect on calcium levels using in vivo multiphoton imaging...
March 21, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28325782/aibp-limits-angiogenesis-thorough-%C3%AE-secretase-mediated-upregulation-of-notch-signaling
#12
Renfang Mao, Shu Meng, Qilin Gu, Raquel Araujo-Gutierrez, Sandeep Kumar, Qing Yan, Felicidad Almazan, Keith A Youker, Yingbin Fu, Henry J Pownall, John P Cooke, Yury I Miller, Longhou Fang
Rationale: Angiogenesis improves perfusion to the ischemic tissue following acute vascular obstruction. Angiogenesis in pathophysiological settings reactivates signaling pathways involved in developmental angiogenesis. We showed previously that apoA-I binding protein (AIBP)-regulated cholesterol efflux in endothelial cells (ECs) controls zebrafish embryonic angiogenesis. Objective: This study is to determine whether loss of AIBP affects angiogenesis in mice during development and under pathological conditions, and to explore the underlying molecular mechanism...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28325286/inclusion-of-the-woodchuck-hepatitis-virus-posttranscriptional-regulatory-element-enhances-aav2-driven-transduction-of-mouse-and-human-retina
#13
Maria I Patrício, Alun R Barnard, Harry O Orlans, Michelle E McClements, Robert E MacLaren
The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) has been included in the transgene cassette of adeno-associated virus (AAV) in several gene therapy clinical trials, including those for inherited retinal diseases. However, the extent to which WPRE increases transgene expression in the retina is still unclear. To address this question, AAV2 vectors containing a reporter gene with and without WPRE were initially compared in vitro and subsequently in vivo by subretinal delivery in mice...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28324222/bdnf-mrna-splice-variants-differentially-impact-ca1-and-ca3-dendrite-complexity-and-spine-morphology-in-the-hippocampus
#14
Kristen R Maynard, John W Hobbs, Mahima Sukumar, Alisha S Kardian, Dennisse V Jimenez, Robert J Schloesser, Keri Martinowich
Brain-derived neurotrophic factor (BDNF) is an activity-dependent neurotrophin critical for neuronal plasticity in the hippocampus. BDNF is encoded by multiple transcripts with alternative 5' untranslated regions (5'UTRS) that display activity-induced targeting to distinct subcellular compartments. While individual Bdnf 5'UTR transcripts influence dendrite morphology in cultured hippocampal neurons, it is unknown whether Bdnf splice variants impact dendrite arborization in functional classes of neurons in the intact hippocampus...
March 21, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28324027/follistatin-targets-distinct-pathways-to-promote-brown-adipocyte-characteristics-in-brown-and-white-adipose-tissues
#15
Rajan Singh, Melissa Braga, Srinivasa T Reddy, Se-Jin Lee, Meher Parveen, Victor Grijalva, Laurent Vergnes, Shehla Pervin
We previously demonstrated that Fst expression is highest in brown adipose tissue (BAT) and skeletal muscle, but is also present at substantial levels in epididymal (Epi) and subcutaneous (SC) white adipose tissues (WAT). Fst promotes mouse brown preadipocyte differentiation and promotes browning during differentiation of mouse embryonic fibroblasts (MEFs). Fst-transgenic (Fst-Tg) mouse show significant increase in circulating Fst levels and increased brown adipose mass. BAT of Fst-Tg mice had increased expression of brown adipose-associated markers including uncoupling protein 1 (UCP1), PRDM16, PGC-1α and Glut4...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#16
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323915/insulin-igf-1-and-gh-receptors-are-altered-in-an-adipose-tissue-depot-specific-manner-in-male-mice-with-modified-gh-action
#17
Rikke Hjortebjerg, Darlene E Berryman, Ross Comisford, Stuart J Frank, Edward O List, Mette Bjerre, Jan Frystyk, John J Kopchick
Growth hormone (GH) is an important determinant of glucose homeostasis and adipose tissue (AT) function. Using seven-month-old bovine GH transgenic (bGH) mice and GH receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression patterns of proteins involved in the interrelated signaling pathways of GH, insulin-like growth factor-1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice that may explain why GH effects depend on AT location...
February 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323022/astrocyte-heme-oxygenase-1-reduces-mortality-and-improves-outcome-after-collagenase-induced-intracerebral-hemorrhage
#18
Jing Chen-Roetling, Pramod Kamalapathy, Yang Cao, Wei Song, Hyman M Schipper, Raymond F Regan
Pharmacotherapies that increase CNS expression of heme oxygenase-1 (HO-1) and other antioxidant proteins have improved outcome in experimental models of spontaneous intracerebral hemorrhage (ICH). In order to more specifically investigate the relationship between HO-1 and ICH outcome, mice expressing human HO-1 driven by the glial fibrillary acidic protein (GFAP) promoter (GFAP·HMOX1 mice) were tested in a model of in situ parenchymal hemorrhage. Injection of collagenase into the striata of wild-type (WT) mice resulted in a 26...
March 17, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28321439/overexpression-of-parkinson-s-disease-associated-mutation-lrrk2-g2019s-in-mouse-forebrain-induces-behavioral-deficits-and-%C3%AE-synuclein-pathology
#19
Yulan Xiong, Stewart Neifert, Senthilkumar S Karuppagounder, Jeannette N Stankowski, Byoung Dae Lee, Jonathan C Grima, Guanxing Chen, Han Seok Ko, Yunjong Lee, Debbie Swing, Lino Tessarollo, Ted M Dawson, Valina L Dawson
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified as an unambiguous cause of late-onset, autosomal-dominant familial Parkinson's disease (PD) and LRRK2 mutations are the strongest genetic risk factor for sporadic PD known to date. A number of transgenic mice expressing wild-type or mutant LRRK2 have been described with varying degrees of LRRK2-related abnormalities and modest pathologies. None of these studies directly addressed the role of the kinase domain in the changes observed and none of the mice present with robust features of the human disease...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28320965/deficiency-of-a-sulfotransferase-for-sialic-acid-modified-glycans-mitigates-alzheimer-s-pathology
#20
Zui Zhang, Yoshiko Takeda-Uchimura, Tahmina Foyez, Shiori Ohtake-Niimi, Narentuya, Hiroyasu Akatsu, Kazuchika Nishitsuji, Makoto Michikawa, Tony Wyss-Coray, Kenji Kadomatsu, Kenji Uchimura
We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
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