Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan Disease
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Mendeley | Further Information

{"title"=>"Aspartoacylase-LacZ knockin mice: An engineered model of canavan disease", "type"=>"journal", "authors"=>[{"first_name"=>"Nadine", "last_name"=>"Mersmann", "scopus_author_id"=>"37861933500"}, {"first_name"=>"Dmitri", "last_name"=>"Tkachev", "scopus_author_id"=>"56663080900"}, {"first_name"=>"Ruth", "last_name"=>"Jelinek", "scopus_author_id"=>"40561402600"}, {"first_name"=>"Philipp Thomas", "last_name"=>"Röth", "scopus_author_id"=>"40561671900"}, {"first_name"=>"Wiebke", "last_name"=>"Möbius", "scopus_author_id"=>"7004620433"}, {"first_name"=>"Torben", "last_name"=>"Ruhwedel", "scopus_author_id"=>"36500099900"}, {"first_name"=>"Sabine", "last_name"=>"Rühle", "scopus_author_id"=>"40561705000"}, {"first_name"=>"Wolfgang", "last_name"=>"Weber-Fahr", "scopus_author_id"=>"6603037429"}, {"first_name"=>"Alexander", "last_name"=>"Sartorius", "scopus_author_id"=>"6602350236"}, {"first_name"=>"Matthias", "last_name"=>"Klugmann", "scopus_author_id"=>"6602094260"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"21625469", "doi"=>"10.1371/journal.pone.0020336", "sgr"=>"79956307321", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-79956307321", "issn"=>"19326203", "pui"=>"361803756"}, "id"=>"172b7f75-eef7-3793-ac7c-aafcdfc3e345", "abstract"=>"Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial β-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspa(lacZ/+)) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (aspa(lacZ/lacZ)) mutants are ASPA-deficient, show CD-like histopathology and moderate neurological impairment with behavioural deficits that are more pronounced in aspa(lacZ/lacZ) males than females. Non-invasive ultrahigh field proton magnetic resonance spectroscopy revealed increased levels of NAA, myo-inositol and taurine in the aspa(lacZ/lacZ) brain. Spongy degeneration was prominent in hippocampus, thalamus, brain stem, and cerebellum, whereas white matter of optic nerve and corpus callosum was spared. Intracellular vacuolisation in astrocytes coincides with axonal swellings in cerebellum and brain stem of aspa(lacZ/lacZ) mutants indicating that astroglia may act as an osmolyte buffer in the aspa-deficient CNS. In summary, the aspa(lacZ) mouse is an accurate model of CD and an important tool to identify novel aspects of its complex pathology.", "link"=>"http://www.mendeley.com/research/aspartoacylaselacz-knockin-mice-engineered-model-canavan-disease", "reader_count"=>26, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>7, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>3, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>7, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>3, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>15, "Neuroscience"=>3, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Portugal"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/773623"], "description"=>"<p>Spectra were acquired from <i>aspa<sup>+/+</sup></i> and <i>aspa<sup>lacZ/lacZ</sup></i> littermates using a 2×2×3 mm<sup>3</sup> single-voxel PRESS Sequence in the thalamus. Representativ metabolites are marked in the spectra (Cr: Creatine and Phosphocreatine, NAA: NAA+NAAG, Cho: Phosphocholine and Glycerophosphorylcholine, Glu: Glutamate, Gln: Glutamine, mI: Myo-Inositol, Tau: Taurine, Glx: Glu+Gln). For metabolite concentrations see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020336#pone-0020336-t001\" target=\"_blank\">Table 1</a>.</p>", "links"=>[], "tags"=>["genetics and genomics", "physiology", "biotechnology", "Computational biology", "neuroscience", "neurological disorders", "Biochemistry"], "article_id"=>443977, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_1_H_MRS_analysis_/443977", "title"=>"<sup>1</sup>H-MRS analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 01:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/773007"], "description"=>"<p>Representative pictures of Nissl stained brain sections of <i>aspa<sup>+/+</sup></i> (A,C) and <i>aspa<sup>lacZ/lacZ</sup></i> (B,D) mice (4 months). Vacuoles are abundant in forebrain grey matter of cortex and thalamus while white matter of the corpus callosum is spared (B). In the hippocampus, the histopathology is exclusively seen in the pyramidal but not the dentate granule cell layer. Magnifications of thalamic areas show substantial spongy degeneration in the mutant (arrows in D) but not in the control (C). hc, hippocampus; cc, corpus callosum; ctx, cortex; dcl, granule cell layer; pcl, pyramidal cell layer; tha, thalamus. Bars: 400 µm in A,B; 200 µm in C,D.</p>", "links"=>[], "tags"=>["vacuolisation"], "article_id"=>443366, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CNS_vacuolisation_in_aspa_lacZ_lacZ_mutants_/443366", "title"=>"CNS vacuolisation in <i>aspa<sup>lacZ/lacZ</sup></i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 00:56:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/773716"], "description"=>"<p><b>A.</b> Analysis of motor coordination in the rotarod test shows impairment of both female and male <i>aspa<sup>lacZ/lacZ</sup></i> mice compared with their <i>aspa<sup>+/+</sup></i> controls at P90. <b>B.</b> Spontaneous exploratory activity and aspects of anxiety-related behaviour of both sexes and genotypes were tested in an open field for 30 min (see Methods section). Male mutants (n = 8) travelled less and spent more time in the centre than male controls (n = 8). This behaviour is suggestive of impaired exploratory activity and anxiolysis. The behaviour of female mutants (n = 6) did not differ from female controls (n = 7).</p>", "links"=>[], "tags"=>["behavioural", "deficits"], "article_id"=>444074, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g008", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Special_behavioural_deficits_in_male_but_not_female_aspa_lacZ_lacZ_mutants_/444074", "title"=>"Special behavioural deficits in male but not female <i>aspa<sup>lacZ/lacZ</sup></i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 01:07:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/772843"], "description"=>"<p><b>A–D,</b> Representative pictures of β-Galactosidase staining in adult <i>aspa<sup>lacZ/+</sup></i> mouse tissues show activity of the <i>aspa</i> gene in oligodendrocytes of white and grey matter throughout the brain. Abundant staining was detected in white matter tracts in cerebellum and corpus callosum. While in the hippocampus and cortex X-Gal staining was found in oligodendrocyte cell bodies (A), lacZ-positive fibres were detected in the thalamus (B). In the cerebellum, proximal processes and somata of white matter oligodendrocytes were stained (C, D). <b>E</b>–<b>F,</b> Outside the CNS, the cortex of the kidney (E), small intestine (F) and sciatic nerve fibres (G) show intense X-Gal staining. <b>H</b>–<b>J,</b> Confocal detection of ASPA immunoreactivity (H) in cerebellar white matter of an adult Plp-DsRed-1 transgenic mouse expressing the red fluorescent reporter protein (I) in oligodendrocytes <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020336#pone.0020336-Hirrlinger1\" target=\"_blank\">[15]</a>. ASPA is expressed in somata and processes of oligodendrocytes. The pattern of ASPA-immunopositive cells matches the DsRed-expressing oligodendrocytes (J). <b>K</b>–<b>M,</b> Confocal detection of ASPA immunoreactivity in cytosolic domains of wildtype Schwann cells. ASPA is enriched at the paranode (asterisk) and bands of Cajal (arrow heads) and segregates from MBP. <b>N,</b> Q-PCR analysis of aspa mRNA levels in different tissues of adult <i>aspa<sup>+/+</sup></i> mice (n = 6). hc, hippocampus; ctx, cortex; med, medulla; tha, thalamus; wm, white matter. Bars: 500 µm in A,C,E; 200 µm in B, D; 400 µm in F,G; 20 µm in H–J; 10 µm in K–M.</p>", "links"=>[], "tags"=>["cns"], "article_id"=>443210, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_aspa_expression_in_CNS_and_periphery_/443210", "title"=>"Analysis of <i>aspa</i> expression in CNS and periphery.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 00:53:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/773361"], "description"=>"<p>Western blot analysis of PLP, DM20, CNP and MBP levels in whole brain lysates of <i>aspa<sup>+/+</sup></i>, <i>aspa<sup>lacZ/+</sup></i> and <i>aspa<sup>lacZ/lacZ</sup></i> mice (P60, n = 3). Quantification of immunoblots shows statistically significant decreases of all proteins tested in homozygous mutants while the presence of one functional aspa allele is sufficient to preserve protein quantities at control levels. Note: PLP, DM20, and the MBP21.5 kD and MBP18.5/17 kD isoforms were analysed separately.</p>", "links"=>[], "tags"=>["levels", "reduced"], "article_id"=>443723, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g005", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Myelin_protein_levels_are_reduced_in_aspa_lacZ_lacZ_mutants_/443723", "title"=>"Myelin protein levels are reduced in <i>aspa<sup>lacZ/lacZ</sup></i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 01:02:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/772705"], "description"=>"<p><b>A,</b> Genomic structure of the murine <i>aspa</i> locus, which spans 6 exons (black boxes). Homologous recombination of the targeting vector inserts the βgeo cassette (blue box), encoding β-Galactosidase (lacZ), into intron 1 of the intact <i>aspa</i> gene. This cassette is flanked by frt-sites (green circles). Additional loxP sites flank exon 2 (red triangles). The vector includes a DTA cassette for negative selection. In the targeted allele, exon 1 is spliced to the splice acceptor site preceding βgeo, and transcription is terminated at the introduced pA site. The conditional <i>aspa<sup>flox</sup></i> allele is produced by breeding <i>aspa<sup>lacZ</sup></i> mutants to FLP-deleter mice <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020336#pone.0020336-Rodriguez1\" target=\"_blank\">[40]</a> for recombination of the βgeo cassette <i>in vivo</i>. Note that frt and loxP sites are not drawn to scale. βgeo, β-galactosidase-neomycin resistance cassette; SA, splice acceptor; pA, polyadenylation site, DTA, Diphteria toxin gene. <b>B,</b> For Southern blot analysis genomic DNA was digested with SmaI/ApaI. The neo probe (white box in A) detected the expected 7.5 kb band in heterozygotes and homozygotes. <b>C,</b> Genomic PCR of littermates with primers 1 & 3 produces the expected amplicons in <i>aspa<sup>+/+</sup></i> (336 bp), <i>aspa<sup>lacZ/+</sup></i> (387 bp and 336 bp) and <i>aspa<sup>lacZ/lacZ</sup></i> (387 bp) animals. The upstream loxP site was detected by PCR with primers 1 & 2 yielding a 307 bp band. <b>D,</b> Q-RT-PCR using a TaqMan probe for quantification of aspa mRNA levels in brains of <i>aspa<sup>+/+</sup></i>, <i>aspa<sup>lacZ/+</sup></i>, and <i>aspa<sup>lacZ/lacZ</sup></i> mice (n = 3) confirms the attenuation of transcription downstream of exon 2 in the targeted allele. <b>E,</b> Representative Western blot of whole brain lysates of a<i>spa</i><sup>+/+</sup>, <i>aspa<sup>lacZ/+</sup></i> and <i>aspa<sup>lacZ/lacZ</sup></i> mice (aged 4 months, n = 3). The 37 kD protein ASPA was detected in <i>aspa</i><sup>+/+</sup> and <i>aspa<sup>lacZ/+</sup></i> mice but not in <i>aspa<sup>lacZ/lacZ</sup></i> mutants. β-Galactosidase is expressed in <i>aspa<sup>lacZ/+</sup></i> and <i>aspa<sup>lacZ/lacZ</sup></i> brain but not controls. α-Tubulin was used as loading control. <b>F.</b> Representative picture of a male <i>aspa<sup>lacZ/lacZ</sup></i> mutant (asterisk) and an <i>aspa<sup>+/+</sup></i> littermate at P70.</p>", "links"=>[], "tags"=>["mice", "homologous"], "article_id"=>443065, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g001", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_aspa_lacZ_mice_by_homologous_recombination_/443065", "title"=>"Generation of <i>aspa<sup>lacZ</sup></i> mice by homologous recombination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 00:51:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/773491"], "description"=>"<p>Immunohistochemical staining in the thalamus of <i>aspa<sup>+/+</sup></i> controls and <i>aspa<sup>lacZ/lacZ</sup></i> mice showed substantially increased numbers of GFAP-positive astrocytes and Iba-1-positive microglia in the mutants (at 3 months of age). Note that ASPA immunoreactivity is present in the control but not in the mutant. Bars: 25 µm.</p>", "links"=>[], "tags"=>["gliosis"], "article_id"=>443850, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reactive_gliosis_in_aspa_lacZ_lacZ_mice_/443850", "title"=>"Reactive gliosis in <i>aspa<sup>lacZ/lacZ</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 01:04:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/388098", "https://ndownloader.figshare.com/files/388141", "https://ndownloader.figshare.com/files/388170", "https://ndownloader.figshare.com/files/388195"], "description"=>"<div><p>Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial <em>β-Galactosidase</em> (<em>lacZ</em>) gene under the control of the <em>aspa</em> regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (<em>aspa<sup>lacZ/+</sup></em>) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (<em>aspa<sup>lacZ/lacZ</sup></em>) mutants are ASPA-deficient, show CD-like histopathology and moderate neurological impairment with behavioural deficits that are more pronounced in <em>aspa<sup>lacZ/lacZ</sup></em> males than females. Non-invasive ultrahigh field proton magnetic resonance spectroscopy revealed increased levels of NAA, myo-inositol and taurine in the <em>aspa<sup>lacZ/lacZ</sup></em> brain. Spongy degeneration was prominent in hippocampus, thalamus, brain stem, and cerebellum, whereas white matter of optic nerve and corpus callosum was spared. Intracellular vacuolisation in astrocytes coincides with axonal swellings in cerebellum and brain stem of <em>aspa<sup>lacZ/lacZ</sup></em> mutants indicating that astroglia may act as an osmolyte buffer in the aspa-deficient CNS. In summary, the <em>aspa<sup>lacZ</sup></em> mouse is an accurate model of CD and an important tool to identify novel aspects of its complex pathology.</p> </div>", "links"=>[], "tags"=>["aspartoacylase-lacz", "knockin", "engineered", "canavan"], "article_id"=>136630, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0020336.s001", "https://dx.doi.org/10.1371/journal.pone.0020336.s002", "https://dx.doi.org/10.1371/journal.pone.0020336.s003", "https://dx.doi.org/10.1371/journal.pone.0020336.s004"], "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Aspartoacylase_LacZ_Knockin_Mice_An_Engineered_Model_of_Canavan_Disease/136630", "title"=>"Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan Disease", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-05-20 01:50:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/773901"], "description"=>"<p>The standard deviation of the metabolite concentrations (SD) corresponds to the Cramér-Rao lower bounds of the LCModel-fit and is given in %. SD-values below 20% are considered reliable. Error bars are derived through the fit-routine and indicate the quality of individual metabolite measurements. Cr: Creatine and Phosphocreatine, NAA: NAA+NAAG, Cho: Phosphocholine and Glycerophosphorylcholine, Glu: Glutamate, Gln: Glutamine, mI: Myo-Inositol, Tau: Taurine, Glc: Glucose.</p>", "links"=>[], "tags"=>["concentrations", "thalamic", "prefrontal"], "article_id"=>444257, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Metabolite_concentrations_in_the_in_vivo_mouse_brain_measured_with_1_H_MRS_over_a_2_2_3_mm_3_and_3_1_2_2_8_mm_3_volume_of_interest_in_the_thalamic_region_and_the_prefrontal_cortex_respectively_/444257", "title"=>"Metabolite concentrations in the <i>in vivo</i> mouse brain measured with <sup>1</sup>H-MRS over a 2*2*3 mm<sup>3</sup> and 3*1.2*2.8 mm<sup>3</sup> volume of interest in the thalamic region and the prefrontal cortex, respectively.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-20 01:10:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/773171"], "description"=>"<p>Caudal brain stem of controls (<b>A, C, F, G</b>) and <i>aspa<sup>lacZ/lacZ</sup></i> mice (<b>B, D, E, H</b>): Vacuolization is abundant in the dorsal region <i>aspa<sup>lacZ/lacZ</sup></i> mice (solitary tract nu, commissural, SolC) as shown in semithin sections (<b>B</b>) and electron microscopy (<b>H</b>). In the pyramidal tract of mutant mice myelin appears normal, but axonal swellings and degeneration are present (<b>D</b>, asterisks). Axonal swellings as well as hypomyelination were found in the dorsal region with abundant vacuolization (<b>F</b>, asterisk). Cerebellum of controls (<b>I, K, M, O</b>) and <i>aspa<sup>lacZ/lacZ</sup></i> mice (<b>J, L, N, P</b>): In semithin sections of mutant cerebellum, vacuoles are detectable in the white matter (WM), granule cell layer (GL) and in the Purkinje cell layer (<b>J, L</b>). Parallel fibre to Purkinje cell dendrite synapses appear normal (<b>M, N</b>), but in <i>aspa<sup>lacZ/lacZ</sup></i> mice the Bergman glia (BG) is swollen and shows accumulation of electron dense particles (<b>N, P</b>). BG, Bergman glia; CC, central canal; GL, granule cell layer; ML, molecular layer; PC, Purkinje cell; PF, parallel fibre; SolC, solitary tract nu, commissural; WM, white matter. Scale bars: 100 µm (<b>A, B, I, J</b>), 5 µm (<b>K, L</b>), 2 µm (<b>G, H</b>), 1 µm (<b>C, D, O, P</b>), 500 nm (<b>M, N</b>).</p>", "links"=>[], "tags"=>["cerebellum"], "article_id"=>443538, "categories"=>["Biotechnology", "Neuroscience", "Biochemistry", "Physiology", "Biological Sciences", "Genetics"], "users"=>["Nadine Mersmann", "Dmitri Tkachev", "Ruth Jelinek", "Philipp Thomas Röth", "Wiebke Möbius", "Torben Ruhwedel", "Sabine Rühle", "Wolfgang Weber-Fahr", "Alexander Sartorius", "Matthias Klugmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020336.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathology_of_the_brain_stem_and_cerebellum_in_aspa_lacZ_lacZ_mice_/443538", "title"=>"Histopathology of the brain stem and cerebellum in <i>aspa<sup>lacZ/lacZ</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-20 00:58:58"}

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Relative Metric

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