Mutation of SLC35D3 Causes Metabolic Syndrome by Impairing Dopamine Signaling in Striatal D1 Neurons
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{"title"=>"Mutation of SLC35D3 Causes Metabolic Syndrome by Impairing Dopamine Signaling in Striatal D1 Neurons", "type"=>"journal", "authors"=>[{"first_name"=>"Zhe", "last_name"=>"Zhang", "scopus_author_id"=>"56191629900"}, {"first_name"=>"Chan Juan", "last_name"=>"Hao", "scopus_author_id"=>"57198264138"}, {"first_name"=>"Chang Gui", "last_name"=>"Li", "scopus_author_id"=>"56191632500"}, {"first_name"=>"Dong Jie", "last_name"=>"Zang", "scopus_author_id"=>"56677448400"}, {"first_name"=>"Jing", "last_name"=>"Zhao", "scopus_author_id"=>"57191639249"}, {"first_name"=>"Xiao Nan", "last_name"=>"Li", "scopus_author_id"=>"56449741300"}, {"first_name"=>"Ai Hua", "last_name"=>"Wei", "scopus_author_id"=>"30268074800"}, {"first_name"=>"Zong Bo", "last_name"=>"Wei", "scopus_author_id"=>"56486576900"}, {"first_name"=>"Lin", "last_name"=>"Yang", "scopus_author_id"=>"55569854200"}, {"first_name"=>"Xin", "last_name"=>"He", "scopus_author_id"=>"35200896600"}, {"first_name"=>"Xue Chu", "last_name"=>"Zhen", "scopus_author_id"=>"16246797700"}, {"first_name"=>"Xiang", "last_name"=>"Gao", "scopus_author_id"=>"35169335800"}, {"first_name"=>"John R.", "last_name"=>"Speakman", "scopus_author_id"=>"7102300657"}, {"first_name"=>"Wei", "last_name"=>"Li", "scopus_author_id"=>"56768375900"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"24550737", "scopus"=>"2-s2.0-84901744101", "doi"=>"10.1371/journal.pgen.1004124", "sgr"=>"84901744101", "pui"=>"372548519"}, "id"=>"0f1f5c0a-c638-3be7-bb43-a37f29baf85e", "abstract"=>"Obesity is one of the largest health problems facing the world today. Although twin and family studies suggest about two-thirds of obesity is caused by genetic factors, only a small fraction of this variance has been unraveled. There are still large numbers of genes to be identified that cause variations in body fatness and the associated diseases encompassed in the metabolic syndrome (MetS). A locus near a sequence tagged site (STS) marker D6S1009 has been linked to obesity or body mass index (BMI). However, its genetic entity is unknown. D6S1009 is located in the intergenic region between SLC35D3 and NHEG1. Here we report that the ros mutant mice harboring a recessive mutation in the Slc35d3 gene show obesity and MetS and reduced membrane dopamine receptor D1 (D1R) with impaired dopamine signaling in striatal neurons. SLC35D3 is localized to both endoplasmic reticulum (ER) and early endosomes and interacts with D1R. In ros striatal D1 neurons, lack of SLC35D3 causes the accumulation of D1R on the ER to impair its ER exit. The MetS phenotype is reversible by the administration of D1R agonist to the ros mutant. In addition, we identified two mutations in the SLC35D3 gene in patients with MetS, which alter the subcellular localization of SLC35D3. Our results suggest that the SLC35D3 gene, close to the D6S1009 locus, is a candidate gene for MetS, which is involved in metabolic control in the central nervous system by regulating dopamine signaling.", "link"=>"http://www.mendeley.com/research/mutation-slc35d3-causes-metabolic-syndrome-impairing-dopamine-signaling-striatal-d1-neurons", "reader_count"=>32, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>3, "Arts and Humanities"=>1, "Chemistry"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>5}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>3, "India"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1386749"], "description"=>"<p>Mice at 24 weeks of age were used in this study. (<b>A</b>) Immunoblotting of SLC35D3 protein in nine brain sub-regions of wild-type (WT) and <i>ros</i> mice. OB: olfactory bulb, CC: cerebral cortex, HIP: hippocampus, STR: striatum, THA: thalamus, HYP: hypothalamus, SN: substantia nigra, CB: cerebellum, BS: brain stem. (<b>B</b>) Immunoblotting assay showed no expression of SLC35D3 in adipose tissue, pancreas, liver, or skeletal muscle compared with striatum or brain in WT mice. There was no expression of SLC35D3 in any of these tissues in <i>ros</i> mice. β-actin serves as a loading control. (<b>C</b>) The size of adipose from epididymal fat pad of <i>ros</i> mice was normal. (<b>D–F</b>) No apparent fat accumulation was observed in pancreas, liver, or skeletal muscle in <i>ros</i> mice. 200× magnification was applied in the sections with H–E staining.</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "sub-regions", "non-neuronal"], "article_id"=>935277, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SLC35D3_expression_in_brain_sub_regions_and_non_neuronal_tissues_/935277", "title"=>"SLC35D3 expression in brain sub-regions and non-neuronal tissues.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386744"], "description"=>"<p>Mice at 12 weeks of age were used in this study. (<b>A</b>) There was no significant difference in daily food intake between wild-type (WT) (n = 14) and <i>ros</i> mice (n = 15). <i>P</i> = 0.066. (<b>B</b>) The distance traveled during 30 min for <i>ros</i> mice (n = 25) was lower than that for the WT (n = 20). (<b>C</b>) The average movement velocity during 30 min for <i>ros</i> mice (n = 25) was shorter than the WT (n = 20). (<b>D</b>) The total movement duration during 30 min for <i>ros</i> mice (n = 25) was shorter than the WT (n = 20). (<b>E–G</b>) Total energy expenditure (Watts) (E), resting energy expenditure (Watts) by Method 1 (F) and resting energy expenditure (Watts) by Method 2 (G) for WT and <i>ros</i> mice measured at age 8 to 12 weeks (n = 8 per group). WT mice are black symbols and <i>ros</i> mice are white symbols. Fitted linear regressions for each data set are shown. There was a significant effect of body weight and genotype but no interaction in total energy expenditure (ANCOVA: Body weight effect, F<sub>1,13</sub> = 44.85, p<0.001); genotype effect, F<sub>1,13</sub> = 10.47, p = 0.007; interaction, not significant (ns).). There was a significant effect of body weight but no genotype or interaction effect in resting energy expenditure by Method 1 or 2 (Method 1 ANCOVA: Body weight effect, F<sub>1,13</sub> = 8.78, p = .011; genotype effect, F<sub>1,13</sub> = 0.35, p = 0.566; interaction: ns. Method 2 ANCOVA: Body weight effect, F<sub>1,13</sub> = 22.29, p<0.001; genotype effect, F<sub>1,13</sub> = 0.03, p = 0.873; interaction, ns.). *<i>P<</i>0.05, **<i>P<</i>0.01.</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "spontaneous", "locomotor", "resting"], "article_id"=>935272, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g002", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Food_intake_spontaneous_locomotor_activity_and_total_and_resting_energy_expenditure_/935272", "title"=>"Food intake, spontaneous locomotor activity and total and resting energy expenditure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386759"], "description"=>"<p>(<b>A</b>) C-terminal D1R interacted with SLC35D3. Cell lysates with the co-expression of Myc-SLC35D3 and Flag-D1R (or Flag-D1R-NT (1–216aa), or Flag-D1R-CT (217–446aa)) were immunoprecipitated. Both the full-length D1R and the D1R-CT bound with Myc-SLC35D3. (<b>B</b>) N-terminal SLC35D3 interacted with D1R. Cell lysates with the co-expression of Myc-D1R and Flag-SLC35D3 (or Flag-SLC35D3-NT (1–301aa), or Flag-SLC35D3-CT (242–422aa)) were immunoprecipitated. Both the full-length SLC35D3 and the SLC35D3-NT bound with Myc-D1R. (<b>C</b>) Two heterozygous mutations were identified in two patients with MetS. WT: wild-type SLC35D3; MU: mutant SLC35D3. In patient #1, a 3-bp deletion (c.1209_1211delGAA) as underlined led to an in-frame deletion of K404. In patient #2, a 3-bp insertion (c.601_602insCTG) as the arrow indicated led to an in-frame insertion of L201. (<b>D</b>) In HEK293T cells, wild-type SLC35D3 was partially colocalized with EEA1 (early endosome) and SEC61B (ER), without colocalization with LAMP3 (late endosome/lysosome). The ΔK404 and insL201 mutations were mislocalized mainly on late endosomes/lysosomes.</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "interacts", "d1r", "mutations", "subcellular"], "article_id"=>935285, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g006", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SLC35D3_interacts_with_D1R_and_mutations_of_SLC35D3_alter_its_subcellular_distribution_/935285", "title"=>"SLC35D3 interacts with D1R and mutations of <i>SLC35D3</i> alter its subcellular distribution.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386742"], "description"=>"<p>(<b>A</b>) Comparison of <i>ros</i> mouse and wild-type (WT) C3H/HeSnJ mouse at 24 weeks of age. (<b>B</b>) Growth curves of male WT and <i>ros</i> mice. Body weights of <i>ros</i> mice are significantly higher than those of WT starting at 8 weeks. (<b>C</b>) <i>ros</i> mice show significantly increased naso-to-anal body length (10.06±0.09 cm, n = 10) compared with the WT controls (9.47±0.06 cm, n = 10) at 24 weeks of age. (<b>D</b>) Perirenal and epididymal fat pad weight in <i>ros</i> mice (n = 10) are significantly higher than those of the WT (n = 10) respectively at 24 weeks of age. (<b>E–G</b>) Serum levels of cholesterol (Chol), triglycerides (TG) and blood glucose (Gluc) in fasted <i>ros</i> mice (n = 14) are significantly higher than those in WT controls (n = 14) at 24 weeks of age. In <i>ros</i>, mean values of Chol, TG, Gluc are 3.82, 1.0, 11.47 mmol/L, respectively; In WT, mean values of Chol, TG, Gluc are 3.21, 0.62, 8.03 mmol/L, respectively. (<b>H</b>) Plasma insulin levels were increased in non-fasted <i>ros</i> mice (3.62±0.20 ng/ml, n = 3) than in WT (0.87±0.08 ng/ml, n = 3) at 24 weeks of age. (<b>I</b>) Insulin tolerance tests (ITT) showed a tendency of impaired tolerance in <i>ros</i> mice compared with WT mice at 24 weeks of age (n = 3). (<b>J</b>) Glucose tolerance tests (ITT) showed a tendency of impaired tolerance in <i>ros</i> mice compared with WT mice at 24 weeks of age (n = 3). *<i>P<</i>0.05, **<i>P<</i>0.01, ***<i>P</i><0.001.</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "mice", "metabolic"], "article_id"=>935270, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ros_mice_exhibit_features_of_metabolic_syndrome_/935270", "title"=>"<i>Ros</i> mice exhibit features of metabolic syndrome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386756"], "description"=>"<p>(<b>A–D</b>) In HEK293T cells, EGFP-SLC35D3 co-localized with the ER marker SEC61B and the endosome marker EEA1, but not with the Golgi marker GM130 or the lysosome/late endosome marker LAMP3. (<b>E</b>) Representative pictures to show that <b>t</b>he smaller gold-labeled D1R particles (10 nm, arrowheads) and the larger gold-labeled SEC61B particles (ER marker) (15 nm, arrows) are colocalized in <i>ros</i> striatum compared with the particles on different structures in wild-type (WT) under immuno-EM at 12 weeks of age. Scale bar: 200 nm. The percentage of D1R colocalized with SEC61B in <i>ros</i> mutant (19.6%, n = 97) is significantly higher than that in wild-type (WT) (6.8%, n = 74), *<i>P<</i>0.05. (<b>F</b>) Immunoblotting of Optiprep (Biocomp, USA) gradient (5–20%) fractions. One microgram tissue lysates of striatum at 12 weeks of age were separated into 26 fractions. D1R was shifted from plasma membrane (PM: GluR1 as a marker) in fractions 16–25 to intracellular fractions 2–10 mainly in endoplasmic reticulum (ER: BIP as a marker) in <i>ros</i> mice compared with WT mice. IN: lysate input; M: molecular marker.</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "localization", "slc35d3", "trafficking"], "article_id"=>935284, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g005", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Subcellular_localization_of_SLC35D3_protein_and_the_effect_of_SLC35D3_on_trafficking_of_D1R_/935284", "title"=>"Subcellular localization of SLC35D3 protein and the effect of SLC35D3 on trafficking of D1R.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386761", "https://ndownloader.figshare.com/files/1386762", "https://ndownloader.figshare.com/files/1386763"], "description"=>"<div><p>Obesity is one of the largest health problems facing the world today. Although twin and family studies suggest about two-thirds of obesity is caused by genetic factors, only a small fraction of this variance has been unraveled. There are still large numbers of genes to be identified that cause variations in body fatness and the associated diseases encompassed in the metabolic syndrome (MetS). A locus near a sequence tagged site (STS) marker D6S1009 has been linked to obesity or body mass index (BMI). However, its genetic entity is unknown. D6S1009 is located in the intergenic region between <i>SLC35D3</i> and <i>NHEG1</i>. Here we report that the <i>ros</i> mutant mice harboring a recessive mutation in the <i>Slc35d3</i> gene show obesity and MetS and reduced membrane dopamine receptor D1 (D1R) with impaired dopamine signaling in striatal neurons. SLC35D3 is localized to both endoplasmic reticulum (ER) and early endosomes and interacts with D1R. In <i>ros</i> striatal D1 neurons, lack of SLC35D3 causes the accumulation of D1R on the ER to impair its ER exit. The MetS phenotype is reversible by the administration of D1R agonist to the <i>ros</i> mutant. In addition, we identified two mutations in the <i>SLC35D3</i> gene in patients with MetS, which alter the subcellular localization of SLC35D3. Our results suggest that the <i>SLC35D3</i> gene, close to the D6S1009 locus, is a candidate gene for MetS, which is involved in metabolic control in the central nervous system by regulating dopamine signaling.</p></div>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "slc35d3", "causes", "metabolic", "impairing", "dopamine", "striatal", "d1"], "article_id"=>935287, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004124.s001", "https://dx.doi.org/10.1371/journal.pgen.1004124.s002", "https://dx.doi.org/10.1371/journal.pgen.1004124.s003"], "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutation_of_SLC35D3_Causes_Metabolic_Syndrome_by_Impairing_Dopamine_Signaling_in_Striatal_D1_Neurons_/935287", "title"=>"Mutation of SLC35D3 Causes Metabolic Syndrome by Impairing Dopamine Signaling in Striatal D1 Neurons", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386760"], "description"=>"<p>Mice at 24 weeks of age were used in this study. (<b>A</b>) Wild-type (WT) or <i>ros</i> mice (n = 9 per group) received a daily intraperitoneal injection of 20 mg/kg SKF38393 for 12 days and weighed on day 14. Body weights of saline-treated WT or <i>ros</i> mice had no significant changes, whereas body weights of SKF38393-treated WT mice were reduced approximately 7% (from 29.61±0.76 g to 27.5±0.6 g), and body weights of SKF38393-treated <i>ros</i> mice were reduced approximately 13% (from 38.56±0.79 g to 33.39±0.58 g). ***<i>P</i><0.001. (<b>B–D</b>) Compared with saline-treated WT mice (n = 8), SKF38393-treated WT mice (n = 9) exhibit no significant changes of serum levels of triglycerides (TG), cholesterol (Chol) and blood glucose (Gluc). In SKF38393-treated <i>ros</i> mice, serum levels of Chol, TG and Gluc were significantly reduced compared to saline-treated <i>ros</i> littermates. SKF38393 vs. saline, Chol: 3.43±0.08 mmol/L (n = 9) vs. 3.86±0.05 mmol/L (n = 7); TG: 1.29 ± 0.06 mmol/L (n = 8) vs. 1.63±0.01 mmol/L (n = 7); Gluc: 11.7±0.57 mmol/L (n = 9) vs. 14.67±0.46 mmol/L (n = 7). **<i>P</i><0.01. (<b>E</b>) Total distances traveled during the period of 30 min to 60 min after SKF38393 treatment were increased in both WT and <i>ros</i> mice. However, the distance traveled in <i>ros</i> mice was greater than that in WT (***<i>P</i><0.001).</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "skf38393", "serum", "lipids", "wild-type"], "article_id"=>935286, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g007", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_SKF38393_treatment_on_body_weight_loss_serum_lipids_and_glucose_and_activity_of_wild_type_or_ros_mice_/935286", "title"=>"Effect of SKF38393 treatment on body weight loss, serum lipids and glucose, and activity of wild-type or <i>ros</i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1386754"], "description"=>"<p>Mice at 12 weeks of age were used in this study. (<b>A</b>) Immunohistochemical detection of D1R on the coronal brain sections of the striatum. In <i>ros</i> mice, visible immunoreactive cell bodies are present (arrows). Scale bar: 100 µm. (<b>B, C</b>) Representative immuno-EM pictures of D1R-labeled particles on plasma membrane (PM, upper panels) and endomembrane structures (EnM, lower panels) in wild-type (WT) and <i>ros</i> striatal neurons are shown without much difference (B). However, the quantification test revealed that the particles on PM in <i>ros</i> mice (34.0%, n = 103) is significantly lower than that in WT (51.7%, n = 87), **<i>P<</i>0.01. Scale bar: 200 nm. (<b>D</b>) SKF82958–induced cAMP accumulation in striatal membranes prepared from WT and <i>ros</i> mice. As compared with the WT (11.09±0.61 pmol/ml, n = 6), cAMP activity in <i>ros</i> membranes (7.11±0.45 pmol/ml, n = 6) was reduced about 36%. *<i>P</i><0.001. (<b>E</b>) Immunoblot analysis of D1 receptor. <i>left panel</i>, Striatum tissues (20 µg) from WT and <i>ros</i> mice were probed with the monoclonal D1R antibody. β-actin was used as a loading control. The immunoblots shown are representative of three independent experiments. <i>right panel</i>, Normalized percentages of the band intensities shown in <i>left panel</i> are means ± SEM (n = 3). There is no significant difference of total D1R levels between WT and <i>ros</i> mice (<i>P</i>>0.05).</p>", "links"=>[], "tags"=>["genetics", "Molecular genetics", "Gene identification and analysis", "Animal genetics", "membrane", "d1r", "reduced", "Striatonigral"], "article_id"=>935282, "categories"=>["Biological Sciences"], "users"=>["Zhe Zhang", "Chan-Juan Hao", "Chang-Gui Li", "Dong-Jie Zang", "Jing Zhao", "Xiao-Nan Li", "Ai-Hua Wei", "Zong-Bo Wei", "Lin Yang", "Xin He", "Xue-Chu Zhen", "Xiang Gao", "John R. Speakman", "Wei Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004124.g004", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_membrane_D1R_and_its_signaling_are_reduced_in_ros_striatonigral_neurons_/935282", "title"=>"Plasma membrane D1R and its signaling are reduced in <i>ros</i> striatonigral neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-13 04:02:57"}

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Relative Metric

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