Prion Protein (PrP) Knock-Out Mice Show Altered Iron Metabolism: A Functional Role for PrP in Iron Uptake and Transport
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{"title"=>"Prion protein (PrP) knock-out mice show altered iron metabolism: A functional role for PrP in iron uptake and transport", "type"=>"journal", "authors"=>[{"first_name"=>"Ajay", "last_name"=>"Singh", "scopus_author_id"=>"55547111104"}, {"first_name"=>"Qingzhong", "last_name"=>"Kong", "scopus_author_id"=>"55167796100"}, {"first_name"=>"Xiu", "last_name"=>"Luo", "scopus_author_id"=>"7402870345"}, {"first_name"=>"Robert B.", "last_name"=>"Petersen", "scopus_author_id"=>"7201919132"}, {"first_name"=>"Howard", "last_name"=>"Meyerson", "scopus_author_id"=>"6701714064"}, {"first_name"=>"Neena", "last_name"=>"Singh", "scopus_author_id"=>"7404364674"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-67749133712", "sgr"=>"67749133712", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0006115", "pmid"=>"19568430", "isbn"=>"1932-6203", "pui"=>"354999668"}, "id"=>"6dff5e80-2ae2-3433-80d5-91975d30834e", "abstract"=>"Despite overwhelming evidence implicating the prion protein (PrP) in prion disease pathogenesis, the normal function of this cell surface glycoprotein remains unclear. In previous reports we demonstrated that PrP mediates cellular iron uptake and transport, and aggregation of PrP to the disease causing PrP-scrapie (PrP(Sc)) form results in imbalance of iron homeostasis in prion disease affected human and animal brains. Here, we show that selective deletion of PrP in transgenic mice (PrP(KO)) alters systemic iron homeostasis as reflected in hematological parameters and levels of total iron and iron regulatory proteins in the plasma, liver, spleen, and brain of PrP(KO) mice relative to matched wild type controls. Introduction of radiolabeled iron ((59)FeCl(3)) to Wt and PrP(KO) mice by gastric gavage reveals inefficient transport of (59)Fe from the duodenum to the blood stream, an early abortive spike of erythropoiesis in the long bones and spleen, and eventual decreased (59)Fe content in red blood cells and all major organs of PrP(KO) mice relative to Wt controls. The iron deficient phenotype of PrP(KO) mice is reversed by expressing Wt PrP in the PrP(KO) background, demonstrating a functional role for PrP in iron uptake and transport. Since iron is required for essential metabolic processes and is also potentially toxic if mismanaged, these results suggest that loss of normal function of PrP due to aggregation to the PrP(Sc) form induces imbalance of brain iron homeostasis, resulting in disease associated neurotoxicity.", "link"=>"http://www.mendeley.com/research/prion-protein-prp-knockout-mice-show-altered-iron-metabolism-functional-role-prp-iron-uptake-transpo", "reader_count"=>36, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Master"=>4, "Student > Bachelor"=>5, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Master"=>4, "Student > Bachelor"=>5, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>2, "Neuroscience"=>3, "Veterinary Science and Veterinary Medicine"=>1, "Physics and Astronomy"=>1, "Chemistry"=>3, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>1, "France"=>1, "Germany"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/892388"], "description"=>"<p>(A) Immunoblot analysis of Wt and PrP<sup>KO</sup> brain homogenates with PrP specific antibody 8H4 shows the expected glycoforms of PrP in Wt samples migrating between 27–37 kDa, and no reaction with PrP<sup>KO</sup> samples as expected (lanes 1–6). Immunoreaction for ferritin, Tf, and TfR shows significantly less ferritin, and more Tf and TfR levels in PrP<sup>KO</sup> samples compared to Wt controls (lanes 1–6). Reaction for β-actin confirms similar loading of protein. (B) Quantitative estimation of proteins in (A) after normalization with β-actin shows a decrease in ferritin, and an increase in Tf and TfR levels in PrP<sup>KO</sup> samples compared to Wt controls. Values are mean±SEM. *<i>p</i><0.001, **<i>p</i><0.01 relative to Wt. n = 6.</p>", "links"=>[], "tags"=>["homogenates", "mice"], "article_id"=>562843, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Brain_homogenates_of_PrP_KO_mice_show_evidence_of_iron_deficiency_/562843", "title"=>"Brain homogenates of PrP<sup>KO</sup> mice show evidence of iron deficiency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:25:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/892881"], "description"=>"<p>(A) Prussian blue staining of frozen sections shows a prominent reaction in the reticulo-endothelial cells of PrP<sup>KO</sup> and Wt samples. (B) In-gel reaction of homogenates with Ferene-S shows less iron content of PrP<sup>KO</sup> ferritin compared to Wt controls (lanes 1–6). (C) Immunoreaction of homogenates with L-chain specific anti-ferritin antibody shows significantly less expression in PrP<sup>KO</sup> samples compared to Wt controls (lanes 1–6). Re-probing for β-actin confirms that the difference is not an artifact of protein loading (lanes 1–6). (D) Quantification by densitometry after normalization with β-actin shows a significant reduction in the iron content and expression of ferritin in PrP<sup>KO</sup> samples compared to matched Wt controls. Values are mean±SEM, n = 3. *<i>p</i><0.01 relative to Wt.</p>", "links"=>[], "tags"=>["mice", "displays", "phenotype"], "article_id"=>563340, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spleen_of_PrP_KO_mice_displays_a_phenotype_of_iron_deficiency_/563340", "title"=>"Spleen of PrP<sup>KO</sup> mice displays a phenotype of iron deficiency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:28:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/893198"], "description"=>"<p>(A) The 4 hour duodenum samples in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006115#pone-0006115-g005\" target=\"_blank\">Figure 5</a> above were homogenized and separated on a non-denaturing gel followed by autoradiography (lanes 1 and 2). The level of <sup>59</sup>Fe labeled ferritin is significantly higher in the PrP<sup>KO</sup> sample compared to matched Wt control (lanes 1 and 2). Transblotting under native conditions followed by immunoblotting for ferritin confirms the identity of <sup>59</sup>Fe labeled bands as ferritin (lanes 3 and 4). Fractionation of the same samples by SDS-PAGE followed by immunoblotting shows relatively more ferritin in the PrP<sup>KO</sup> sample compared to matched Wt control (lanes 5 and 6). (B) Quantification by densitometry shows significantly more <sup>59</sup>Fe-ferritin and ferritin protein levels in the duodenum of PrP<sup>KO</sup> mice relative to matched Wt controls. Values are mean±SEM, n = 3. *<i>p</i><0.001 relative to Wt.</p>", "links"=>[], "tags"=>["retained", "ferritin", "duodenal", "epithelium"], "article_id"=>563657, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iron_is_retained_within_ferritin_in_the_duodenal_epithelium_of_PrP_KO_mice_/563657", "title"=>"Iron is retained within ferritin in the duodenal epithelium of PrP<sup>KO</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:30:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/893067"], "description"=>"<p>(A) Autoradiogram of upper gastrointestinal tract of Wt and PrP<sup>KO</sup> mice fed 20 µCi of <sup>59</sup>FeCl<sub>3</sub> by gastric gavage shows higher levels of <sup>59</sup>Fe in PrP<sup>KO</sup> samples after 1, 4, 24, and 48 hours of chase (lanes 1–10). The difference becomes more obvious after 11 days of chase (lanes 11 and 12). (Lanes 9 and 10 were exposed for 24 hours and lanes 11 and 12 for 6 days to observe the difference clearly). A representative experiment out of a total of three is shown. (B) Quantification of <sup>59</sup>Fe in the first 10 cm of the duodenum shows significantly higher <sup>59</sup>Fe in the PrP<sup>KO</sup> samples at all time points tested compared to matched Wt controls. Values are mean±SEM, n = 3. *<i>p</i><0.01 as compared to Wt.</p>", "links"=>[], "tags"=>["retained", "duodenum"], "article_id"=>563527, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g005", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iron_is_retained_in_the_duodenum_of_PrP_KO_mice_/563527", "title"=>"Iron is retained in the duodenum of PrP<sup>KO</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:29:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/893802"], "description"=>"<p>Distribution of <sup>59</sup>Fe in the blood, liver, spleen, and femur after 4 hours of chase shows similar incorporation in Wt and PrP<sup>(+)</sup> mice in the organs tested, and significantly more <sup>59</sup>Fe in the spleen and femur of PrP<sup>KO</sup> mice as noted above. One way ANOVA shows a significant difference among Wt, PrP<sup>KO</sup>, and PrP<sup>(+)</sup> samples (p<0.0001). Post hoc Bonferroni tests show significant difference in <sup>59</sup>Fe in littermates PrP<sup>(+)</sup> and PrP<sup>KO</sup> organs relative to Wt controls (*p<0.01; **p<0.05). Littermate PrP<sup>(+)</sup> shows a significant difference compared to PrP<sup>KO</sup> counterpart (#p<0.01). Values are mean±SEM of three independent experiments.</p>", "links"=>[], "tags"=>["hematology/anemias", "infectious diseases/prion diseases", "neurological disorders/prion diseases"], "article_id"=>564264, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g011", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_59_Fe_in_PrP_and_PrP_KO_litter_mates_/564264", "title"=>"Distribution of <sup>59</sup>Fe in PrP<sup>(+)</sup> and PrP<sup>KO</sup> litter-mates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:33:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/893589"], "description"=>"<p>Autoradiogram of Wt and PrP<sup>KO</sup> spleen homogenates separated on a native gel show significantly higher <sup>59</sup>Fe-ferritin and <sup>59</sup>Fe-Tf in the PrP<sup>KO</sup> sample after 4 hours of chase (lanes 3 and 4). At other time points Wt samples show higher levels of <sup>59</sup>Fe in ferritin and Tf bands relative to PrP<sup>KO</sup> samples (lanes 1 and 2 and 5–8). (The identity of ferritin and Tf bands was confirmed by immunoblotting <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006115#pone.0006115-Singh1\" target=\"_blank\">[13]</a>).</p>", "links"=>[], "tags"=>["uptake", "wt"], "article_id"=>564053, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g009", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kinetics_of_59_Fe_uptake_by_Wt_and_PrP_KO_spleen_/564053", "title"=>"Kinetics of <sup>59</sup>Fe uptake by Wt and PrP<sup>KO</sup> spleen.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:32:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/892524"], "description"=>"<p>(A) Incubation of unfixed brain sections with FITC-Tf shows significantly more binding to the Purkinje cell neurons of PrP<sup>KO</sup> sample compared to Wt controls (panels 1 and 2) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006115#pone.0006115-Moos2\" target=\"_blank\">[16]</a>. Pre-incubation of brain sections with unlabeled apo-Tf decreases the signal significantly in both samples (panels 3 and 4), demonstrating the specificity of binding. The assay was performed on three sections each from three different sets of mice. A representative section is shown. (B) Autoradiograph of brain sections prepared from Wt and PrP<sup>KO</sup> mice injected with <sup>59</sup>FeCl<sub>3</sub> intravenously shows significantly more <sup>59</sup>Fe in PrP<sup>KO</sup> sections compared to Wt controls (panels 1–4). A scan of brain sections exposed to the film in panels 2 and 4 respectively is shown (panels 5 and 6). (Two consecutive 700 µM sections from each brain sample are shown. <sup>59</sup>Fe is visible as radio-opaque black dots.</p>", "links"=>[], "tags"=>["sections", "mice", "tfr"], "article_id"=>562982, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Brain_sections_of_PrP_KO_mice_show_up_regulation_of_TfR_and_increased_transport_of_iron_from_the_blood_stream_/562982", "title"=>"Brain sections of PrP<sup>KO</sup> mice show up regulation of TfR and increased transport of iron from the blood stream.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:26:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/893891"], "description"=>"<p>Values are mean±SEM of cells plated in triplicate from two different sets of mice. <sup>*</sup><i>p</i><0.01 compared to Wt.</p>", "links"=>[], "tags"=>["peritoneal", "macrophages", "18"], "article_id"=>564347, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.t002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Release_of_59_Fe_from_peritoneal_macrophages_after_18_hours_/564347", "title"=>"Release of <sup>59</sup>Fe from peritoneal macrophages after 18 hours.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 05:33:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/893482"], "description"=>"<p>(A): Equal volume Wt and PrP<sup>KO</sup> plasma collected at different time points of chase were separated on a non-denaturing gel followed by autoradiography. After 1 hour of chase, <sup>59</sup>Fe-Tf in the PrP<sup>KO</sup> sample is lower than matched Wt controls (lanes 1 and 2). However, the ratio reverses thereafter, and the level of <sup>59</sup>Fe-Tf in the PrP<sup>KO</sup> sample is higher than Wt controls after 4, 24, and 48 hours of chase (lanes 3–8). (B) RBCs of Wt mice show minimal levels of <sup>59</sup>Fe after 1 and 4 hours, and significant increase after 24 and 48 hours of chase. PrP<sup>KO</sup> mice, on the other hand, show iron counts at 4 hours, and minimal increase thereafter.</p>", "links"=>[], "tags"=>["wt"], "article_id"=>563946, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g008", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_course_of_59_Fe_distribution_in_the_blood_of_Wt_and_PrP_KO_mice_/563946", "title"=>"Time course of <sup>59</sup>Fe distribution in the blood of Wt and PrP<sup>KO</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:31:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/893696"], "description"=>"<p>(A) Immunoblot analysis of Wt and littermate PrP<sup>KO</sup> and PrP<sup>(+)</sup> brain homogenates for PrP shows the expected glycoforms of PrP in Wt and PrP<sup>(+)</sup> samples (lanes 1 and 3), and no reaction in the PrP<sup>KO</sup> sample as expected (lane 2). (B) Autoradiogram of the upper gastrointestinal tract of Wt and littermate PrP<sup>(+)</sup> and PrP<sup>KO</sup> mice fed <sup>59</sup>FeCl<sub>3</sub> by gastric gavage as above and chased for 4 hours shows significantly more <sup>59</sup>Fe in the PrP<sup>KO</sup> sample relative to Wt control (lanes 2 and 4). Notably, the <sup>59</sup>Fe content of PrP<sup>(+)</sup> duodenum is similar to Wt, and significantly less than the littermate PrP<sup>KO</sup> sample (lanes 1, 3 and 4). (C) Quantification of <sup>59</sup>Fe in the first 10 cm of the duodenum shows significantly more <sup>59</sup>Fe in the PrP<sup>KO</sup> sample compared to matched Wt control. Similarly, more <sup>59</sup>Fe is detected in the PrP<sup>KO</sup> sample compared littermate PrP<sup>(+)</sup> control. One way ANOVA shows a significant difference in <sup>59</sup>Fe incorporation between Wt and PrP<sup>KO</sup>, Wt and littermate PrP<sup>KO</sup>, PrP<sup>(+)</sup> and littermate PrP<sup>KO</sup>, and PrP<sup>KO</sup> and PrP<sup>(+)</sup> (<i>p</i><0.0001). Post hoc Bonferroni tests show significant difference in <sup>59</sup>Fe in PrP<sup>KO</sup> as well as littermate PrP<sup>(+)</sup> and PrP<sup>KO</sup> duodenums compared to Wt control (*<i>p</i><0.01; #<i>p</i><0.05). PrP<sup>(+)</sup> exhibit significant difference compared to PrP<sup>KO</sup> ($<i>p</i><0.01), and littermate PrP<sup>(+)</sup> and PrP<sup>KO</sup> also differ significantly (@p<0.01). Values are mean±SEM, n = 3.</p>", "links"=>[], "tags"=>["deficiency", "mice", "reversed", "expressing", "wt"], "article_id"=>564152, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g010", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iron_deficiency_in_PrP_KO_mice_is_reversed_by_expressing_Wt_PrP_/564152", "title"=>"Iron deficiency in PrP<sup>KO</sup> mice is reversed by expressing Wt PrP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:32:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/893350"], "description"=>"<p>Plasma: <sup>59</sup>Fe in PrP<sup>KO</sup> samples is lower after 1 hour, increases by 48 hours, and falls to values below Wt after 11 days of chase. RBCs: Wt RBCs show <sup>59</sup>Fe incorporation after 24 hours, and the amount increases steadily till 11 days of chase. PrP<sup>KO</sup> RBCs, on the other hand, incorporate <sup>59</sup>Fe relatively sooner after 4 hours, and show only a modest increase till 11 days of chase. Except for the 4 hour chase time, the amount of <sup>59</sup>Fe in PrP<sup>KO</sup> RBCs is significantly lower than Wt controls, especially after 11 days of chase. Spleen: Wt samples show a slight increase in <sup>59</sup>Fe after 24 hours, and minimal change thereafter. PrP<sup>KO</sup> spleens, on the other hand, show a significant increase after 4 hours, followed by a precipitous fall after 24 hours. Femur: Kinetics of <sup>59</sup>Fe uptake mirrors that of the spleen. PrP<sup>KO</sup> samples show a spike at 4 hours that is maintained till 24 hours, followed by a fall. Wt samples show a delayed peak at 24 hours, and a fall to similar levels as the PrP<sup>KO</sup> sample after 11 days. Liver: Wt samples show a steady increase in <sup>59</sup>Fe till 11 days of chase. PrP<sup>KO</sup> samples, on the other hand, show a peak at 24 hours, and the counts fall thereafter to values significantly lower than Wt controls. Brain: Wt and PrP<sup>KO</sup> samples do not show much difference at early time points of chase, but <sup>59</sup>Fe incorporation in the PrP<sup>KO</sup> sample is significantly lower than Wt controls after 11 days of chase. Values are mean±SEM of three independent experiments. *<i>p</i><0.01, **<i>p</i><0.001 relative to Wt.</p>", "links"=>[], "tags"=>["wt"], "article_id"=>563813, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g007", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_59_Fe_in_Wt_and_PrP_KO_mice_/563813", "title"=>"Distribution of <sup>59</sup>Fe in Wt and PrP<sup>KO</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:30:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/892716"], "description"=>"<p>(A) Prussian blue staining of frozen sections shows minimal reaction for iron in the PrP<sup>KO</sup> sample compared to Wt controls. (B) In-gel reaction of homogenates with Ferene-S shows significantly less iron content of PrP<sup>KO</sup> ferritin compared to Wt controls (lanes 1–4). (C) Immunoreaction of homogenates with anti-ferritin antibody specific for H and L chains shows significantly less ferritin expression in PrP<sup>KO</sup> samples compared to Wt controls (lanes 1–6). Re-probing for Tf shows an increase in Tf expression in PrP<sup>KO</sup> samples relative to Wt controls (lanes 1–6). Levels of β-actin are similar in all samples, confirming that the observed differences are not an artifact of protein loading (lanes 1–6). (D) Quantification by densitometry shows a significant reduction in the iron content and expression of ferritin, and an increase in Tf expression in PrP<sup>KO</sup> samples compared to matched Wt controls. Values are mean±SEM, n = 3. *<i>p</i><0.001 relative to Wt.</p>", "links"=>[], "tags"=>["mice", "displays", "phenotype"], "article_id"=>563172, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Liver_of_PrP_KO_mice_displays_a_phenotype_of_iron_deficiency_/563172", "title"=>"Liver of PrP<sup>KO</sup> mice displays a phenotype of iron deficiency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 05:27:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/893920"], "description"=>"<p>Values are mean±SEM. <sup>*</sup><i>p</i><0.001, <sup>**</sup><i>p</i><0.01, <sup>***</sup><i>p</i><0.05 as compared to Wt. NS: not significant; N: number of animals in each group; RBCs: red blood cells; TIBC: total iron binding capacity; Tf: transferrin; ↓: decrease; ↑: increase.</p>", "links"=>[], "tags"=>["parameters", "wt"], "article_id"=>564379, "categories"=>["Computational Biology", "Neuroscience", "Medicine"], "users"=>["Ajay Singh", "Qingzhong Kong", "Xiu Luo", "Robert B. Petersen", "Howard Meyerson", "Neena Singh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006115.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hematological_parameters_in_Wt_and_PrP_KO_mice_/564379", "title"=>"Hematological parameters in Wt and PrP<sup>KO</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 05:34:05"}

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Relative Metric

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