Validation of a P-Glycoprotein (P-gp) Humanized Mouse Model by Integrating Selective Absolute Quantification of Human MDR1, Mouse Mdr1a and Mdr1b Protein Expressions with In Vivo Functional Analysis for Blood-Brain Barrier Transport
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{"title"=>"Validation of a P-Glycoprotein (P-gp) humanized mouse model by integrating selective absolute quantification of human MDR1, mouse Mdr1a and Mdr1b protein expressions with in vivo functional analysis for blood-brain barrier transport", "type"=>"journal", "authors"=>[{"first_name"=>"Muhammad Waqas", "last_name"=>"Sadiq", "scopus_author_id"=>"36982103000"}, {"first_name"=>"Yasuo", "last_name"=>"Uchida", "scopus_author_id"=>"22959123200"}, {"first_name"=>"Yutaro", "last_name"=>"Hoshi", "scopus_author_id"=>"55674638900"}, {"first_name"=>"Masanori", "last_name"=>"Tachikawa", "scopus_author_id"=>"35330981600"}, {"first_name"=>"Tetsuya", "last_name"=>"Terasaki", "scopus_author_id"=>"7102734642"}, {"first_name"=>"Margareta", "last_name"=>"Hammarlund-Udenaes", "scopus_author_id"=>"7003449143"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0118638", "issn"=>"19326203", "pui"=>"604276387", "pmid"=>"25932627", "sgr"=>"84929103984", "scopus"=>"2-s2.0-84929103984"}, "id"=>"35e6d6e2-eb90-3c45-8225-a6d585fd0f10", "abstract"=>"It is essential to establish a useful validation method for newly generated humanized mouse models. The novel approach of combining our established species-specific protein quantification method combined with in vivo functional studies is evaluated to validate a humanized mouse model of P-gp/MDR1 efflux transporter. The P-gp substrates digoxin, verapamil and docetaxel were administered to male FVB Mdr1a/1b(+/+) (FVB WT), FVB Mdr1a/1b(-/-) (Mdr1a/1b(-/-)), C57BL/6 Mdr1a/1b(+/+) (C57BL/6 WT) and humanized C57BL (hMDR1) mice. Brain-to-plasma total concentration ratios (Kp) were measured. Quantitative targeted absolute proteomic (QTAP) analysis was used to selectively quantify the protein expression levels of hMDR1, Mdr1a and Mdr1b in the isolated brain capillaries. The protein expressions of other transporters, receptors and claudin-5 were also quantified. The Kp for digoxin, verapamil, and docetaxel were 20, 30 and 4 times higher in the Mdr1a/1b(-/-) mice than in the FVB WT controls, as expected. The Kp for digoxin, verapamil and docetaxel were 2, 16 and 2-times higher in the hMDR1 compared to the C57BL/6 WT mice. The hMDR1 mice had 63- and 9.1-fold lower expressions of the hMDR1 and Mdr1a proteins than the corresponding expression of Mdr1a in C57BL/6 WT mice, respectively. The protein expression levels of other molecules were almost consistent between C57BL/6 WT and hMDR1 mice. The P-gp function at the BBB in the hMDR1 mice was smaller than that in WT mice due to lower protein expression levels of hMDR1 and Mdr1a. The combination of QTAP and in vivo functional analyses was successfully applied to validate the humanized animal model and evaluates its suitability for further studies.", "link"=>"http://www.mendeley.com/research/validation-pglycoprotein-pgp-humanized-mouse-model-integrating-selective-absolute-quantification-hum", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>7, "Veterinary Science and Veterinary Medicine"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2048323"], "description"=>"<p>Digoxin was administered subcutaneously at a dose of 1 mg/kg. P-gp blockers were given as cyclosporine A 100 mg/kg intraperitoneally, quinidine 50 mg/kg intraperitoneally, verapamil 3 mg/kg subcutaneously or elacridar 3 mg/kg subcutaneously, one hour before the digoxin administration.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401024, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.g005", "stats"=>{"downloads"=>4, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_K_p_values_of_digoxin_in_C57BL_6_WT_n_5_for_each_group_grey_bars_and_hMDR1_mice_n_5_black_bars_in_the_presence_of_different_blockers_p_lt_0_05_/1401024", "title"=>"K<sub>p</sub> values of digoxin in C57BL/6 WT (n = 5 for each group) (grey bars) and hMDR1 mice (n = 5) (black bars) in the presence of different blockers (* p < 0.05).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048325"], "description"=>"<p>Oxycodone was administered 1 mg/kg subcutaneously. The P-gp blockers were given cyclosporine A 100 mg/kg intraperitoneally, verapamil 3 mg/kg or elacridar 6 mg/kg subcutaneously one hour before the administration of oxycodone.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401026, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.g006", "stats"=>{"downloads"=>2, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_different_P_gp_blockers_on_oxycodone_K_p_in_C57BL_6_WT_mice_n_20_p_lt_0_05_p_lt_0_01_/1401026", "title"=>"Effect of different P-gp blockers on oxycodone K<sub>p</sub> in C57BL/6 WT mice (n = 20), (* p < 0.05, ** p < 0.01).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048326"], "description"=>"<p>The first column represents the drug studied in the presence of cyclosporine A.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401027, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.t002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cyclosporine_A_concentrations_956_g_ml_in_blood_of_the_different_groups_of_mice_/1401027", "title"=>"Cyclosporine A concentrations (μg/ml) in blood of the different groups of mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048327"], "description"=>"<p>(* No variability on ratio as mean K<sub>p</sub> values were used to calculate it).</p><p>The ratio<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118638#t003fn001\" target=\"_blank\">*</a></sup> of K<sub>p</sub> with blocker/K<sub>p</sub> in control mice for digoxin, representing a difference in the effect of the blockers between C57BL/6 WT and hMDR1 mice.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401028, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.t003", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_K_p_with_blocker_K_p_in_control_mice_for_digoxin_representing_a_difference_in_the_effect_of_the_blockers_between_C57BL_6_WT_and_hMDR1_mice_/1401028", "title"=>"The ratio<sup>*</sup> of K<sub>p</sub> with blocker/K<sub>p</sub> in control mice for digoxin, representing a difference in the effect of the blockers between C57BL/6 WT and hMDR1 mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048329"], "description"=>"<p>Blood levels of the blockers used when studying digoxin transport in C57BL/6 WT and hMDR1 mice.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401030, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.t004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blood_levels_of_the_blockers_used_when_studying_digoxin_transport_in_C57BL_6_WT_and_hMDR1_mice_/1401030", "title"=>"Blood levels of the blockers used when studying digoxin transport in C57BL/6 WT and hMDR1 mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048330"], "description"=>"<p>Brain capillary was isolated from the pooled frozen brains of 10 mice by means of nylon mesh method. Brain capillary passing through an 85 μm nylon mesh and retained on a 20 μm nylon mesh was collected, and digested with lysyl endopeptidase and trypsin. The digest was subjected to LC-MS/MS analysis with internal standard peptides. The each target peptide was monitored with four different SRM/MRM transitions. The preparation of pooled brain capillary from 10 mice was conducted only one time. For the pooled brain capillary, the digestion followed by LC-MS/MS analysis was repeated three times. The protein expression level of target molecule was determined as an average and variability (mean ± S.E.M.) of the quantitative values obtained from different SRM/MRM transitions in three analyses. Therefore, the S.E.M. represents the variability of protein expression level determined in different MS/MS transitions in three analyses, but does not represent the inter-individual variability.</p><p>U.L.Q., under the limit of quantification.</p><p>*<i>p</i> < 0.01, significantly different from the C57BL/6 WT mice.</p><p><sup>a</sup> measured by using a peptide probe set specific for human MDR1.</p><p><sup>b</sup> measured by using a peptide probe set specific for mouse mdr1a.</p><p><sup>c</sup> measured by using a peptide probe set common for human MDR1 and mouse mdr1a.</p><p>Protein expression levels of membrane proteins in brain capillaries isolated from C57BL/6 WT and hMDR1 mice.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401031, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.t005", "stats"=>{"downloads"=>6, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_expression_levels_of_membrane_proteins_in_brain_capillaries_isolated_from_C57BL_6_WT_and_hMDR1_mice_/1401031", "title"=>"Protein expression levels of membrane proteins in brain capillaries isolated from C57BL/6 WT and hMDR1 mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048331"], "description"=>"<div><p>It is essential to establish a useful validation method for newly generated humanized mouse models. The novel approach of combining our established species-specific protein quantification method combined with in vivo functional studies is evaluated to validate a humanized mouse model of P-gp/MDR1 efflux transporter. The P-gp substrates digoxin, verapamil and docetaxel were administered to male FVB Mdr1a/1b(+/+) (FVB WT), FVB Mdr1a/1b(-/-) (Mdr1a/1b(-/-)), C57BL/6 Mdr1a/1b(+/+) (C57BL/6 WT) and humanized C57BL (hMDR1) mice. Brain-to-plasma total concentration ratios (K<sub>p</sub>) were measured. Quantitative targeted absolute proteomic (QTAP) analysis was used to selectively quantify the protein expression levels of hMDR1, Mdr1a and Mdr1b in the isolated brain capillaries. The protein expressions of other transporters, receptors and claudin-5 were also quantified. The K<sub>p</sub> for digoxin, verapamil, and docetaxel were 20, 30 and 4 times higher in the Mdr1a/1b(-/-) mice than in the FVB WT controls, as expected. The K<sub>p</sub> for digoxin, verapamil and docetaxel were 2, 16 and 2-times higher in the hMDR1 compared to the C57BL/6 WT mice. The hMDR1 mice had 63- and 9.1-fold lower expressions of the hMDR1 and Mdr1a proteins than the corresponding expression of Mdr1a in C57BL/6 WT mice, respectively. The protein expression levels of other molecules were almost consistent between C57BL/6 WT and hMDR1 mice. The P-gp function at the BBB in the hMDR1 mice was smaller than that in WT mice due to lower protein expression levels of hMDR1 and Mdr1a. The combination of QTAP and in vivo functional analyses was successfully applied to validate the humanized animal model and evaluates its suitability for further studies.</p></div>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401032, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638", "stats"=>{"downloads"=>6, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Validation_of_a_P_Glycoprotein_P_gp_Humanized_Mouse_Model_by_Integrating_Selective_Absolute_Quantification_of_Human_MDR1_Mouse_Mdr1a_and_Mdr1b_Protein_Expressions_with_In_Vivo_Functional_Analysis_for_Blood_Brain_Barrier_Transport/1401032", "title"=>"Validation of a P-Glycoprotein (P-gp) Humanized Mouse Model by Integrating Selective Absolute Quantification of Human MDR1, Mouse Mdr1a and Mdr1b Protein Expressions with <i>In Vivo</i> Functional Analysis for Blood-Brain Barrier Transport", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048317"], "description"=>"<p>Stages for the development of P-gp hMDR1 mice described in different steps during which both <i>Mdr1a</i> and <i>Mdr1b</i> were knocked out from mouse DNA and replaced by human <i>MDR1</i>.</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401018, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stages_for_the_development_of_P_gp_hMDR1_mice_described_in_different_steps_during_which_both_Mdr1a_and_Mdr1b_were_knocked_out_from_mouse_DNA_and_replaced_by_human_MDR1_/1401018", "title"=>"Stages for the development of P-gp hMDR1 mice described in different steps during which both <i>Mdr1a</i> and <i>Mdr1b</i> were knocked out from mouse DNA and replaced by human <i>MDR1</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048318"], "description"=>"<p>The doses of 1 mg/kg for digoxin and verapamil were administered subcutaneously while 10mg/kg of docetaxel was administered in tail-vein as a slow injection over five minutes due to its irritating character (n = 5 for each group).</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401019, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.g002", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_K_p_between_the_Mdr1a_1b_mice_with_FVB_WT_controls_and_hMDR1_mice_with_the_C57BL_6_WT_controls_for_digoxin_A_verapamil_B_and_docetaxel_C_p_lt_0_05_p_lt_0_01_/1401019", "title"=>"Comparison of K<sub>p</sub> between the Mdr1a/1b(-/-) mice with FVB WT controls and hMDR1 mice with the C57BL/6 WT controls for digoxin (A) verapamil (B) and docetaxel (C) (* p < 0.05, ** p < 0.01).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048319"], "description"=>"<p>Oxycodone was administered 1 mg/kg subcutaneously (n = 3).</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401020, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.g003", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_K_p_between_the_Mdr1a_1b_mice_with_FVB_WT_controls_and_hMDR1_mice_with_C57BL_6_WT_controls_for_oxycodone_p_lt_0_05_p_lt_0_01_/1401020", "title"=>"Comparison of K<sub>p</sub> between the Mdr1a/1b(-/-) mice with FVB WT controls and hMDR1 mice with C57BL/6 WT controls for oxycodone (* p < 0.05, ** p < 0.01).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-01 03:16:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/2048322"], "description"=>"<p>Cyclosporine A was administered intraperitoneally one hour before the drugs at a dose of 100 mg/kg (n = 5 for each group).</p>", "links"=>[], "tags"=>["humanized mouse model", "Mdr 1a", "hMDR 1 mice", "FVB WT controls", "humanized mouse models", "protein expression levels", "FVB Mdr 1a", "QTAP", "hMDR 1", "C 57BL WT", "humanized C 57BL", "humanized animal model", "bbb", "C 57BL WT mice", "Mdr 1a mice", "Mdr 1a C 57BL Mdr 1a", "Vivo Functional Analysis", "Mdr 1a proteins", "Mdr 1b Protein Expressions"], "article_id"=>1401023, "categories"=>["Biological Sciences"], "users"=>["Muhammad Waqas Sadiq", "Yasuo Uchida", "Yutaro Hoshi", "Masanori Tachikawa", "Tetsuya Terasaki", "Margareta Hammarlund-Udenaes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118638.g004", "stats"=>{"downloads"=>2, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_K_p_between_the_Mdr1a_1b_mice_with_FVB_WT_controls_and_hMDR1_mice_with_C57BL_6_WT_controls_with_their_wild_type_for_verapamil_A_and_docetaxel_B_in_the_presence_of_cyclosporine_A_p_lt_0_05_p_lt_0_01_/1401023", "title"=>"Comparison of K<sub>p</sub> between the Mdr1a/1b(-/-) mice with FVB WT controls and hMDR1 mice with C57BL/6 WT controls with their wild type for verapamil (A) and docetaxel (B) in the presence of cyclosporine A (* p < 0.05, ** p < 0.01).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-01 03:16:27"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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