Página 1 dos resultados de 9824 itens digitais encontrados em 0.028 segundos

‣ CCP1/Nna1 functions in protein turnover in mouse brain: Implications for cell death in Purkinje cell degeneration mice

BEREZNIUK, Iryna; SIRONI, Juan; CALLAWAY, Myrasol B.; CASTRO, Leandro M.; HIRATA, Izaura Y.; FERRO, Emer S.; FRICKER, Lloyd D.
Fonte: FEDERATION AMER SOC EXP BIOL Publicador: FEDERATION AMER SOC EXP BIOL
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.208086%
Purkinje cell degeneration (pcd) mice have a mutation within the gene encoding cytosolic carboxypeptidase 1 (CCP1/Nna1), which has homology to metallocarboxypeptidases. To assess the function of CCP1/Nna1, quantitative proteomics and peptidomics approaches were used to compare proteins and peptides in mutant and wild-type mice. Hundreds of peptides derived from cytosolic and mitochondrial proteins are greatly elevated in pcd mouse hypothalamus, amygdala, cortex, prefrontal cortex, and striatum. However, the major proteins detected on 2-D gel electrophoresis were present in mutant and wild-type mouse cortex and hypothalamus at comparable levels, and proteasome activity is normal in these brain regions of pcd mice, suggesting that the increase in cellular peptide levels in the pcd mice is due to reduced degradation of the peptides downstream of the proteasome. Both nondegenerating and degenerating regions of pcd mouse brain, but not wild-type mouse brain, show elevated autophagy, which can be triggered by a decrease in amino acid levels. Taken together with previous studies on CCP1/Nna1, these data suggest that CCP1/Nna1 plays a role in protein turnover by cleaving proteasome-generated peptides into amino acids and that decreased peptide turnover in the pcd mice leads to cell death.-Berezniuk...

‣ Caracterização fenotípica do camundongo BALB/c mutante anêmico; Phenotype characterization of anemic mutant BALB/c mouse

Miyashiro, Samantha Ive
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 28/09/2012 Português
Relevância na Pesquisa
47.148037%
Várias linhagens de camundongos resultam de mutações genéticas pontuais espontâneas ou induzidas e estas alterações podem apresentar fenótipos relevantes semelhantes a doenças hereditárias humanas. Massironi et al. (2006) desenvolveram vários camundongos BALB/c mutantes com o agente mutagênico etil-nitroso-uréia (ENU) no Biotério de Experimentação do Departamento de Imunologia do Instituto de Ciências Biomédicas (ICB) da Universidade de São Paulo. Destes, o mutante chamado anêmico foi objeto de estudo desta pesquisa, que tem como objetivo a sua fenotipagem. A avaliação hematológica revelou moderada anemia com intensa policromasia e reticulocitose, acompanhada de anisocitose, macrocitose, hipocromia, inclusões intraeritrocíticas e corpúsculos de Heinz, do nascimento até 18 meses de idade. Apresentaram também hemoglobinúria, bilirrubinemia, hiperfosfatemia e populações eritrocíticas com diferentes resistências à lise osmótica. No estudo da hemoglobina, não foi possível distinguir Hb anormal pela eletroforese em acetato-celulose em pH alcalino, ou cadeia globínica diferente pela eletroforese de cadeias globínicas em pH alcalino, mas constatou-se precipitação da hemoglobina no teste de estabilidade térmica e no teste de isopropanol. Na necrópsia...

‣ Traveling stripes on the skin of a mutant mouse

Suzuki, Noboru; Hirata, Masashi; Kondo, Shigeru
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.096025%
In the course of animal development, complex structures form autonomously from the apparently shapeless egg. How cells can produce spatial patterns that are much larger than each cell is one of the key issues in developmental biology. It has been suggested that spatial patterns in animals form through the same principles by which dispatched structures are formed in the nonbiological system. However, because of the complexity of biological systems, molecular details of such phenomena have been rarely clarified. In this article, we introduce an example of a pattern-forming phenomenon that occurs in the skin of mutant mice. The mutant mouse has a defect in splicing of the Foxn1 (Whn or nude) gene, which terminates hair follicle development just after pigment begins to accumulate in the follicle. The immature follicles are rapidly discharged, and a new hair cycle resumes. Eventually, the skin color of the mouse appears to oscillate. The color oscillation is synchronous in juvenile mice, but the phase gradually shifts among skin regions to eventually form traveling, evenly spaced stripes. Although the time scale is quite different, the pattern change in the mutant mouse shares characteristics with the nonlinear waves generated on excitable media...

‣ Molecular cloning of the cDNA for a mutant mouse ribonucleotide reductase M1 that produces a dominant mutator phenotype in mammalian cells.

Caras, I W; Martin, D W
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1988 Português
Relevância na Pesquisa
47.02257%
Mammalian ribonucleotide reductase is regulated by the binding of dATP and other nucleotide effectors to allosteric sites on subunit M1. Using mRNA from a mutant mouse T-lymphoma (S49) cell line, we have isolated a cDNA which encodes an altered, dATP feedback-resistant subunit M1. The mutant cDNA contains a single point mutation (a G-to-A transition) at codon 57, converting aspartic acid to asparagine. Proof that this mutation is responsible for the phenotype of dATP feedback resistance is provided by the following evidence. (i) The mutation was detected only in mutant S49 cells containing dATP feedback-resistant ribonucleotide reductase and not in wild-type or other mutant S49 cells. (ii) Transfection of Chinese hamster ovary cells with an expression plasmid containing the mutant M1 cDNA resulted in the production of dATP feedback-resistant ribonucleotide reductase. Transfected CHO cells expressing the mutant M1 cDNA exhibited a 15- to 25-fold increase in the frequency of spontaneous mutation to 6-thioguanine resistance, confirming that dATP feedback-resistant ribonucleotide reductase produces a mutator phenotype in mammalian cells. The availability of a cDNA which encodes dATP feedback-resistant subunit M1 thus provides a means of manipulating by transfection the frequency of spontaneous mutation in mammalian cells.

‣ Oogenesis defects in a mutant mouse model of oculodentodigital dysplasia

Tong, Dan; Colley, Deanne; Thoo, Renee; Li, Tony Y.; Plante, Isabelle; Laird, Dale W.; Bai, Donglin; Kidder, Gerald M.
Fonte: The Company of Biologists Limited Publicador: The Company of Biologists Limited
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.044795%
The essential role of connexin43 (Cx43) during oogenesis has been demonstrated by the severe germ cell deficiency and arrested folliculogenesis observed in Cx43 knockout mice. Recently, another mutant mouse strain became available (Gja1Jrt/+) that carries the dominant loss-of-function Cx43 mutation, Cx43G60S. Gja1Jrt/+ mice display features of the human disease oculodentodigital dysplasia (ODDD), which is caused by mutations in the GJA1 gene. We used this new mutant strain to study how a disease-linked Cx43 mutant affects oogenesis. We found that female mutant mice are subfertile with significantly reduced mating success and small litters. The phosphorylated species of the Cx43 protein are reduced in the mutant ovaries in association with impaired trafficking and assembly of gap junctions in the membranes of granulosa cells, confirming that the mutant protein acts dominantly on its wild-type counterpart. Correspondingly, although starting with a normal abundance of germ cells, ovaries of the mutant mice contain significantly fewer pre-ovulatory follicles and do not respond to superovulation by gonadotropins, which is at least partially the result of reduced proliferation and increased apoptosis of granulosa cells. We conclude that the Gja1Jrt mutation has a dominant negative effect on Cx43 function in the ovary...

‣ Patterned Neuroprotection in the Inpp4awbl Mutant Mouse Cerebellum Correlates with the Expression of Eaat4

Sachs, Andrew J.; David, Samuel A.; Haider, Neena B.; Nystuen, Arne M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 14/12/2009 Português
Relevância na Pesquisa
47.075107%
The weeble mutant mouse has a frame shift mutation in inositol polyphosphate 4-phosphatase type I (Inpp4a). The phenotype is characterized by an early onset cerebellar ataxia and neurodegeneration, especially apparent in the Purkinje cells. Purkinje cell loss is a common pathological finding in many human and mouse ataxic disorders. Here we show that in the Inpp4awbl mutant, Purkinje cells are lost in a specific temporal and spatial pattern. Loss occurs early in postnatal development; however, prior to the appearance of climbing fibers in the developing molecular layer, the mutant has a normal complement of Purkinje cells and they are properly positioned. Degeneration and reactive gliosis are present at postnatal day 5 and progress rapidly in a defined pattern of patches; however, Inpp4a is expressed uniformly across Purkinje cells. In late stage mutants, patches of surviving Purkinje cells appear remarkably normal with the exception that the climbing fibers have been excessively eliminated. Surviving Purkinje cells express Eaat4, a glutamate transporter that is differentially expressed in subsets of Purkinje cells during development and into adult stages. Prior to Purkinje cell loss, reactive gliosis and dendritic atrophy can be seen in Eaat4 negative stripes. Our data suggest that Purkinje cell loss in the Inpp4awbl mutant is due to glutamate excitotoxicity initiated by the climbing fiber...

‣ Cytoarchitectural disruption of the superior colliculus and an enlarged acoustic startle response in the Tuba1a mutant mouse

Edwards, A.; Treiber, C.D.; Breuss, M.; Pidsley, R.; Huang, G.-J.; Cleak, J.; Oliver, P.L.; Flint, J.; Keays, D.A.
Fonte: Elsevier Science Publicador: Elsevier Science
Tipo: Artigo de Revista Científica
Publicado em 10/11/2011 Português
Relevância na Pesquisa
47.02309%
The Jenna mutant mouse harbours an S140G mutation in Tuba1a that impairs tubulin heterodimer formation resulting in defective neuronal migration during development. The consequence of decreased neuronal motility is a fractured pyramidal cell layer in the hippocampus and wave-like perturbations in the cerebral cortex. Here, we extend our characterisation of this mouse investigating the laminar architecture of the superior colliculus (SC). Our results reveal that the structure of the SC in mutant animals is intact; however, it is significantly thinner with an apparent fusion of the intermediate grey and white layers. Birthdate labelling at E12.5 and E13.5 showed that the S140G mutation impairs the radial migration of neurons in the SC. A quantitative assessment of neuronal number in adulthood reveals a massive reduction in postmitotic neurons in mutant animals, which we attribute to increased apoptotic cell death. Consistent with the role of the SC in modulating sensorimotor gating, and the circuitry that modulates this behaviour, we find that Jenna mutants exhibit an exaggerated acoustic startle response. Our results highlight the importance of Tuba1a for correct neuronal migration and implicate postnatal apoptotic cell death in the pathophysiological mechanisms underlying the tubulinopathies.

‣ A phenotype survey of 36 mutant mouse strains with gene-targeted defects in glycosyltransferases or glycan-binding proteins

Orr, Sally L; Le, Dzung; Long, Jeffrey M; Sobieszczuk, Peter; Ma, Bo; Tian, Hua; Fang, Xiaoqun; Paulson, James C; Marth, Jamey D; Varki, Nissi
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.197446%
The consortium for functional glycomics (CFG) was a large research initiative providing networking and resources for investigators studying the role of glycans and glycan-binding proteins in health and disease. Starting in 2001, six scientific cores were established to generate data, materials and new technologies. By the end of funding in 2011, the mouse phenotype core (MPC) submitted data to a website from the phenotype screen of 36 mutant mouse strains deficient in a gene for either a glycan-binding protein (GBP) or glycosyltransferase (GT). Each mutant strain was allotted three months for analysis and screened by standard phenotype assays used in the fields of immunology, histology, hematology, coagulation, serum chemistry, metabolism and behavior. Twenty of the deficient mouse strains had been studied in other laboratories, and additional tests were performed on these strains to confirm previous observations and discover new data. The CFG constructed 16 new homozygous mutant mouse strains and completed the initial phenotype screen of the majority of these new mutant strains. In total, >300 phenotype changes were observed, but considering the over 100 assays performed on each strain, most of the phenotypes were unchanged. Phenotype differences include abnormal testis morphology in GlcNAcT9- and Siglec-H-deficient mice and lethality in Pomgnt1-deficient mice. The numerous altered phenotypes discovered...

‣ Characterization of Gap Junction Proteins in the Bladder of Cx43 Mutant Mouse Models of Oculodentodigital Dysplasia

Lorentz, R.; Shao, Q.; Huang, T.; Fishman, G. I.; Laird, D. W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.185605%
Oculodentodigital dysplasia (ODDD) is a rare developmental disease resulting from germline mutations in the GJA1 gene that encodes the gap junction protein connexin43 (Cx43). In addition to the classical ODDD symptoms that affect the eyes, teeth, bone and digits, in some cases ODDD patients have reported bladder impairments. Thus, we chose to characterize the bladder in mutant mouse models of ODDD that harbor two distinct Cx43 mutations, G60S and I130T. Histological assessment revealed no difference in bladder detrusor wall thickness in mutant compared to littermate control mice. The overall localization of Cx43 in the lamina propria and detrusor also appeared to be similar in the bladders of mutant mice with the exception that the G60S mice had more instances of intra-cellular Cx43. However, both mutant mouse lines exhibited a significant reduction in the phosphorylated P1 and P2 iso-forms of Cx43, while only the I130T mice exhibited a reduction in total Cx43 levels. Interestingly, Cx26 levels and distribution were not altered in mutant mice as it was localized to intracellular compartments and restricted to the basal cell layers of the urothelium. Our studies suggest that these two distinct genetically modified mouse models of ODDD probably mimic patients who lack bladder defects or other factors...

‣ INFRAFRONTIER—providing mutant mouse resources as research tools for the international scientific community

Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.152417%
The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques.

‣ Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines

Horsch, Marion; Aguilar-Pimentel, Juan Antonio; Bönisch, Clemens; Côme, Christophe; Kolster-Fog, Cathrine; Jensen, Klaus T.; Lund, Anders H.; Lee, Icksoo; Grossman, Lawrence I.; Sinkler, Christopher; Hüttemann, Maik; Bohn, Erwin; Fuchs, Helmut; Ollert,
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 11/08/2015 Português
Relevância na Pesquisa
47.299097%
We established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immunological and transcriptome data from GMC phenotyping screens under standard conditions. Applying these criteria we identified a few from several hundred mutant mouse lines and further characterized the Cox4i2tm1Hutt, Ifit2tm1.1Ebsb, and Prdm11tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition to an altered airway inflammatory response under OVA challenge conditions. Similar selection strategies may be used for the analysis of additional genotype – envirotype interactions for other diseases.

‣ Cleft palate pathogenesis in mutant mouse models

Liu, Han (1978 - ); Jiang, Rulang
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado Formato: Number of Pages:xii, 142 leaves
Português
Relevância na Pesquisa
47.40354%
Thesis (Ph. D.)--University of Rochester. Dept. of Biology, 2009.; Craniofacial malformations, including cleft lip and cleft palate, are among the most common birth defects in humans, affecting 1 in 500 to 2500 live births worldwide. Both genetic and environmental factors may contribute to these defects. Extensive studies have been carried out to investigate the mechanisms of normal craniofacial development and to explore the pathogenesis of craniofacial malformations. For my Ph.D. thesis work, I have chosen the Twirler mutant mouse as a model system to study the genetic and molecular mechanisms of cleft palate. Twirler (Tw) is a spontaneous mutation that caused cleft lip with cleft palate (CL/P) or cleft palate only (CP) in homozygous mutant mice. Histological analyses revealed obviously smaller palate shelves in the Tw mutant mice during early palate growth, and failure of palate shelf elevation at later stages. Significantly reduced cell proliferation was detected within the palatal mesenchyme of the mutant palate shelves, which may contribute to the growth defect of the palate shelves observed. Tw was originally mapped to mouse Chromosome 18 (Lyon 1958; 1975; Lane et al., 1981; Griffith et al., 1996). By using an inter-sub specific genetic mapping strategy...

‣ Étude du rôle de Pax6 dans la gliogenèse

Cannizzaro, Enrica
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
Relevância na Pesquisa
47.21401%
Les astrocytes sont des cellules gliales présentes dans le système nerveux central, qui exercent de nombreuses fonctions physiologiques essentielles et sont impliquées dans la réponse aux lésions et dans plusieurs pathologies du cerveau. Les astrocytes sont générés par les cellules de la glie radiale, les précurseurs communs de la plupart des cellules neuronales et gliales du cerveau, après le début de la production des neurones. Le passage de la neurogenèse à la gliogenèse est le résultat de mécanismes moléculaires complexes induits par des signaux intrinsèques et extrinsèques responsables du changement de propriété des précurseurs et de leur spécification. Le gène Pax6 code pour un facteur de transcription hautement conservé, impliqué dans plusieurs aspects du développement du système nerveux central, tels que la régionalisation et la neurogenèse. Il est exprimé à partir des stades les plus précoces dans les cellules neuroépithéliales (les cellules souches neurales) et dans la glie radiale, dérivant de la différenciation de ces cellules. L’objectif de cette étude est d’analyser le rôle de Pax6 dans la différenciation et dans le développement des astrocytes. À travers l’utilisation d’un modèle murin mutant nul pour Pax6...

‣ INFRAFRONTIER--providing mutant mouse resources as research tools for the international scientific community

Meehan, T.F.; Demengeot, Jocelyne; 44 colaborators, Infrafrontier Consortium
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 03/11/2014 Português
Relevância na Pesquisa
47.152417%
The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI).

‣ Tauopathic Changes in the Striatum of A53T α-Synuclein Mutant Mouse Model of Parkinson's Disease

Wills, Jonathan; Credle, Joel; Haggerty, Thomas; Lee, Jae-Hoon; Oaks, Adam W.; Sidhu, Anita
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 21/03/2011 Português
Relevância na Pesquisa
47.112676%
Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins...

‣ Mutant Mouse Models: Genotype-Phenotype Relationships to Negative Symptoms in Schizophrenia

O'Tuathaigh, Colm M. P.; Kirby, Brian P.; Moran, Paula M.; Waddington, John L.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
67.075107%
Negative symptoms encompass diminution in emotional expression and motivation, some of which relate to human attributes that may not be accessible readily in animals. Additionally, their refractoriness to treatment precludes therapeutic validation of putative models. This review considers critically the application of mutant mouse models to the study of the pathobiology of negative symptoms. It focuses on 4 main approaches: genes related to the pathobiology of schizophrenia, genes associated with risk for schizophrenia, neurodevelopmental-synaptic genes, and variant approaches from other areas of neurobiology. Despite rapid advances over the past several years, it is clear that we continue to face substantive challenges in applying mutant models to better understand the pathobiology of negative symptoms: the majority of evidence relates to impairments in social behavior, with only limited data relating to anhedonia and negligible data concerning avolition and other features; even for the most widely examined feature, social behavior, studies have used diverse assessments thereof; modelling must proceed in cognizance of increasing evidence that genes and pathobiologies implicated in schizophrenia overlap with other psychotic disorders...

‣ Mutant Mouse Models: Phenotypic Relationships to Domains of Psychopathology and Pathobiology in Schizophrenia

O'Tuathaigh, Colm M. P.; Waddington, John L.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
56.827793%
The present series of review articles seeks to elaborate how current findings in mutant mice may inform on the relationship between candidate genes and individual psychopathological and pathobiological aspects of schizophrenia. Each of the authors focuses on an overlapping selection of both well-characterized and emergent candidate genes, as identified through association and linkage studies and/or via their involvement in putative pathophysiological mechanisms, particularly those relating to dopaminergic and glutamatergic processes.

‣ A Novel Bone Morphogenetic Protein 2 Mutant Mouse, nBmp2NLStm, Displays Impaired Intracellular Ca2+ Handling in Skeletal Muscle

Bridgewater, Laura C.; Mayo, Jaime L.; Evanson, Bradley G.; Whitt, Megan E.; Dean, Spencer A.; Yates, Joshua D.; Holden, Devin N.; Schmidt, Alina D.; Fox, Christopher L.; Dhunghel, Saroj; Steed, Kevin S.; Adam, Michael M.; Nichols, Caitlin A.; Loganathan,
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.075107%
We recently reported a novel form of BMP2, designated nBMP2, which is translated from an alternative downstream start codon and is localized to the nucleus rather than secreted from the cell. To examine the function of nBMP2 in the nucleus, we engineered a gene-targeted mutant mouse model (nBmp2NLStm) in which nBMP2 cannot be translocated to the nucleus. Immunohistochemistry demonstrated the presence of nBMP2 staining in the myonuclei of wild type but not mutant skeletal muscle. The nBmp2NLStm mouse exhibits altered function of skeletal muscle as demonstrated by a significant increase in the time required for relaxation following a stimulated twitch contraction. Force frequency analysis showed elevated force production in mutant muscles compared to controls from 10 to 60 Hz stimulation frequency, consistent with the mutant muscle's reduced ability to relax between rapidly stimulated contractions. Muscle relaxation after contraction is mediated by the active transport of Ca2+ from the cytoplasm to the sarcoplasmic reticulum by sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), and enzyme activity assays revealed that SERCA activity in skeletal muscle from nBmp2NLStm mice was reduced to approximately 80% of wild type. These results suggest that nBMP2 plays a role in the establishment or maintenance of intracellular Ca2+ transport pathways in skeletal muscle.

‣ Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain.

Rawal, N; Lee, Y J; Paik, W K; Kim, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/11/1992 Português
Relevância na Pesquisa
47.14543%
The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN'G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found in MBP; however, their relative concentrations varied significantly with the age of the animal. The amounts of MeArg and Me2(sym)Arg in MBP increased as a function of the age of the brain, whereas that of Me2(asym)Arg decreased. MBP from early-myelinating mouse brain was shown to contain a high proportion of Me2(asym)Arg, which was hardly detectable in older brain MBP. This derivative, Me2(asym)Arg, was also absent from MBP embedded in the most compact multilamellar myelin, but was present in MBP in the least compact myelin (P3B). Comparing the extent of total methylation in vivo (sum of all three arginine derivatives), MBP extracted from less-compact myelin (P3A and P3B) showed a level approx. 40% higher than that from compact myelin. MBPs isolated from dysmyelinating mutant mouse brains...

‣ Gzalpha deficient mice: enzyme levels in the autonomic nervous system, neuronal survival and effect of genetic background

Powell, Kim; Matthaei, Klaus; Heydon, Katharina; Hendry, Ian
Fonte: Pergamon-Elsevier Ltd Publicador: Pergamon-Elsevier Ltd
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.97955%
Our laboratory has generated a genetically mutant mouse in which the alpha subunit of the heterotrimeric GTP binding protein, Gz has been made dysfunctional by homologous recombination to determine its in vivo function. These animals show a characteristic failure to thrive phenotype. Gzα is expressed in a variety of nervous system tissues as well as in the adrenal medulla. We therefore examined the autonomic nervous system of the Gzα deficient mouse by measuring the activity of tyrosine hydroxylase and choline acetyltransferase in the superior cervical ganglia, submaxillary gland and the adrenal medulla. Preliminary results using animals of mixed BALB/c and C57BL/6 strains gave inconsistent results. Further experiments demonstrated differences in the activity of tyrosine hydroxylase and choline acetyltransferase between BALB/c and C57BL/6 mouse strains. The analysis of the pure strains showed a reduction in the size and enzyme levels of the adrenal gland and submaxillary glands of the Gzα deficient mouse suggesting a role for adrenal insufficiency and/or nutritional disorders for the failure to thrive phenotype. The survival of sympathetic and sensory neurons was also examined in the Gzα deficient mouse and in the presence of pertussis toxin...