Identification of Stim1 as a Candidate Gene for Exaggerated Sympathetic Response to Stress in the Stroke-Prone Spontaneously Hypertensive Rat
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{"title"=>"Identification of stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat", "type"=>"journal", "authors"=>[{"first_name"=>"Mohammed Zubaerul", "last_name"=>"Ferdaus", "scopus_author_id"=>"36070418700"}, {"first_name"=>"Bing", "last_name"=>"Xiao", "scopus_author_id"=>"37666514500"}, {"first_name"=>"Hiroki", "last_name"=>"Ohara", "scopus_author_id"=>"55803650700"}, {"first_name"=>"Kiyomitsu", "last_name"=>"Nemoto", "scopus_author_id"=>"7201791216"}, {"first_name"=>"Yuji", "last_name"=>"Harada", "scopus_author_id"=>"7401827994"}, {"first_name"=>"Kathrin", "last_name"=>"Saar", "scopus_author_id"=>"7003288074"}, {"first_name"=>"Norbert", "last_name"=>"Hubner", "scopus_author_id"=>"7003749232"}, {"first_name"=>"Minoru", "last_name"=>"Isomura", "scopus_author_id"=>"7004538530"}, {"first_name"=>"Toru", "last_name"=>"Nabika", "scopus_author_id"=>"56243671900"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0095091", "pui"=>"607990585", "sgr"=>"84922393933", "scopus"=>"2-s2.0-84922393933", "issn"=>"19326203", "pmid"=>"24736434", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"62017552-0e76-369b-93ed-fd46b25c9624", "abstract"=>"The stroke-prone spontaneously hypertensive rat (SHRSP) is known to have exaggerated sympathetic nerve activity to various types of stress, which might contribute to the pathogenesis of severe hypertension and stroke observed in this strain. Previously, by using a congenic strain (called SPwch1.72) constructed between SHRSP and the normotensive Wistar-Kyoto rat (WKY), we showed that a 1.8-Mbp fragment on chromosome 1 (Chr1) of SHRSP harbored the responsible gene(s) for the exaggerated sympathetic response to stress. To further narrow down the candidate region, in this study, another congenic strain (SPwch1.71) harboring a smaller fragment on Chr1 including two functional candidate genes, Phox2a and Ship2, was generated. Sympathetic response to cold and restraint stress was compared among SHRSP, SPwch1.71, SPwch1.72 and WKY by three different methods (urinary norepinephrine excretion, blood pressure measurement by the telemetry system and the power spectral analysis on heart rate variability). The results indicated that the response in SPwch1.71 did not significantly differ from that in SHRSP, excluding Phox2a and Ship2 from the candidate genes. As the stress response in SPwch1.72 was significantly less than that in SHRSP, it was concluded that the 1.2-Mbp congenic region covered by SPwch1.72 (and not by SPwch1.71) was responsible for the sympathetic stress response. The sequence analysis of 12 potential candidate genes in this region in WKY/Izm and SHRSP/Izm identified a nonsense mutation in the stromal interaction molecule 1 (Stim1) gene of SHRSP/Izm which was shared among 4 substrains of SHRSP. A western blot analysis confirmed a truncated form of STIM1 in SHRSP/Izm. In addition, the analysis revealed that the protein level of STIM1 in the brainstem of SHRSP/Izm was significantly lower when compared with WKY/Izm. Our results suggested that Stim1 is a strong candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP.", "link"=>"http://www.mendeley.com/research/identification-stim1-candidate-gene-exaggerated-sympathetic-response-stress-strokeprone-spontaneousl", "reader_count"=>3, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>2, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>2, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1465657", "https://ndownloader.figshare.com/files/1465658", "https://ndownloader.figshare.com/files/1465659", "https://ndownloader.figshare.com/files/1465660"], "description"=>"<div><p>The stroke-prone spontaneously hypertensive rat (SHRSP) is known to have exaggerated sympathetic nerve activity to various types of stress, which might contribute to the pathogenesis of severe hypertension and stroke observed in this strain. Previously, by using a congenic strain (called SPwch1.72) constructed between SHRSP and the normotensive Wistar-Kyoto rat (WKY), we showed that a 1.8-Mbp fragment on chromosome 1 (Chr1) of SHRSP harbored the responsible gene(s) for the exaggerated sympathetic response to stress. To further narrow down the candidate region, in this study, another congenic strain (SPwch1.71) harboring a smaller fragment on Chr1 including two functional candidate genes, <i>Phox2a</i> and <i>Ship2,</i> was generated. Sympathetic response to cold and restraint stress was compared among SHRSP, SPwch1.71, SPwch1.72 and WKY by three different methods (urinary norepinephrine excretion, blood pressure measurement by the telemetry system and the power spectral analysis on heart rate variability). The results indicated that the response in SPwch1.71 did not significantly differ from that in SHRSP, excluding <i>Phox2a</i> and <i>Ship2</i> from the candidate genes. As the stress response in SPwch1.72 was significantly less than that in SHRSP, it was concluded that the 1.2-Mbp congenic region covered by SPwch1.72 (and not by SPwch1.71) was responsible for the sympathetic stress response. The sequence analysis of 12 potential candidate genes in this region in WKY/Izm and SHRSP/Izm identified a nonsense mutation in the stromal interaction molecule 1 (<i>Stim1</i>) gene of SHRSP/Izm which was shared among 4 substrains of SHRSP. A western blot analysis confirmed a truncated form of STIM1 in SHRSP/Izm. In addition, the analysis revealed that the protein level of STIM1 in the brainstem of SHRSP/Izm was significantly lower when compared with WKY/Izm. Our results suggested that <i>Stim1</i> is a strong candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP.</p></div>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "exaggerated", "sympathetic", "stroke-prone", "spontaneously", "hypertensive"], "article_id"=>1000300, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0095091.s001", "https://dx.doi.org/10.1371/journal.pone.0095091.s002", "https://dx.doi.org/10.1371/journal.pone.0095091.s003", "https://dx.doi.org/10.1371/journal.pone.0095091.s004"], "stats"=>{"downloads"=>4, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Identification_of_Stim1_as_a_Candidate_Gene_for_Exaggerated_Sympathetic_Response_to_Stress_in_the_Stroke_Prone_Spontaneously_Hypertensive_Rat/1000300", "title"=>"Identification of <i>Stim1</i> as a Candidate Gene for Exaggerated Sympathetic Response to Stress in the Stroke-Prone Spontaneously Hypertensive Rat", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-04-15 04:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1465654"], "description"=>"<p>Baseline blood pressure (BP), heart rate (HR), increase in BP (<i>Δ</i>BP), HR (<i>Δ</i>HR), LF/HF (<i>Δ</i>LF/HF, a parameter for the relative sympathetic activity), and changes in urinary norepinephrine excretion (<i>Δ</i>NE) under cold and restraint stress in SHRSP were compared with those in SPwch1.71,SPwch1.72 and WKY <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095091#pone.0095091-Xiao1\" target=\"_blank\">[5]</a>. The numbers of rats used for each analysis are shown in parentheses. *<i>P</i><0.05 vs. SHRSP by Dunnett’s post-hoc test.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "congenic"], "article_id"=>1000297, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095091.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_stress_response_in_the_congenic_strains_/1000297", "title"=>"Evaluation of stress response in the congenic strains.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-15 04:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1465652"], "description"=>"<p>Five rats of the each strain were used. Ventrolateral part of the brainstem including RVLM was dissected and RNA was extracted. Relative levels of gene expression were evaluated by quantitative RT-PCR analysis. The expression levels of each gene were normalized with β-actin mRNA. Each column shows the expression level of WKY and SHRSP under the room temperature (RT) or under the cold stress (Cold) as indicated in the panel for <i>Nup98</i>. SP: SHRSP, *<i>P</i><0.05 vs. WKY under the cold stress by Student’s t-test.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "genes", "brainstem", "wky"], "article_id"=>1000295, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095091.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_analysis_of_candidate_genes_in_the_brainstem_of_WKY_and_SHRSP_/1000295", "title"=>"Expression analysis of candidate genes in the brainstem of WKY and SHRSP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-15 04:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1465653"], "description"=>"<p>A) Western blotting was performed as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095091#s2\" target=\"_blank\">Materials and Methods</a>. The size of STIM1 in SHRSP was obviously smaller than that in WKY. A representative data is shown. B) Semi-quantitative evaluation of the STIM1 protein level was performed using ImageJ software. The relative amount of STIM1 was standardized with the level of β-actin. Room temp: room temperature, *<i>P</i><0.05 vs. WKY by Student’s t-test.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "blot"], "article_id"=>1000296, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095091.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_analysis_of_STIM1_/1000296", "title"=>"Western blot analysis of STIM1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-15 04:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1465648"], "description"=>"<p>Closed columns indicate the regions transferred from the WKY genome. Vertical lines on the both ends of the columns show intervals including recombination breakpoints. Supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095091#pone.0095091.s004\" target=\"_blank\">Table S3</a> is available for further information about the candidate genes. Genomic position of each simple sequence repeat marker and SNPs in the <i>Trpc2</i>, <i>Art5</i> and <i>Olr111</i> are defined based on RGSC Genome Assembly v3.4.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "congenic", "genes"], "article_id"=>1000291, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095091.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_map_of_the_congenic_region_and_candidate_genes_located_in_the_region_/1000291", "title"=>"Genetic map of the congenic region and candidate genes located in the region.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-15 04:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1465656"], "description"=>"<p>Genomic position of each SNP is defined based on RGSC Genome Assembly v3.4.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "variations"], "article_id"=>1000299, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095091.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allelic_difference_of_the_two_sequence_variations_identified_in_Stim1_in_various_rat_strains_/1000299", "title"=>"Allelic difference of the two sequence variations identified in <i>Stim1</i> in various rat strains.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-15 04:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1465655"], "description"=>"<p>*The genomic position of SNP is defined based on the RGSC Genome Assembly v3.4.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Vascular medicine", "blood pressure", "hypertension", "cardiology", "research design", "Clinical research design", "Animal models of disease", "substitutions", "genes", "chromosome"], "article_id"=>1000298, "categories"=>["Biological Sciences"], "users"=>["Mohammed Zubaerul Ferdaus", "Bing Xiao", "Hiroki Ohara", "Kiyomitsu Nemoto", "Yuji Harada", "Kathrin Saar", "Norbert Hubner", "Minoru Isomura", "Toru Nabika"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095091.t002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nonsynonymous_substitutions_identified_in_candidate_genes_located_in_a_1_8_Mbp_region_on_chromosome_1_/1000298", "title"=>"Nonsynonymous substitutions identified in candidate genes located in a 1.8-Mbp region on chromosome 1.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-15 04:02:49"}

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