The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
John R. Strauss - One of the best experts on this subject based on the ideXlab platform.
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases.
Molecular pharmacology, 2011Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, Sarah Beth Horwitz, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, John R. StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Pharmacokinetic studies with the Mdr1a P-gp substRates loperamide, indinavir, and talinolol indicated that Mdr1a was functionally inactive in the blood-brain barrier and intestine in Mdr1a(-/-) Rats. To identify possible compensatory mechanisms in Mdr1a(-/-) Rats, the expression levels of drug-metabolizing enzyme and transporter-related genes were compared in brain, liver, kidney, and intestine of male and female Mdr1a(-/-) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(-/-) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(-/-) Rat will be a valuable tool for central nervous system drug target validation and determining the role of P-gp in drug absorption and disposition.
Xiaoyan Chu - One of the best experts on this subject based on the ideXlab platform.
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases. Mol Pharmacol 81:220–227
2012Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, Sarah Horwitz, John StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Phar-macokinetic studies with the Mdr1a P-gp substRates lopera-mide, indinavir, and talinolol indicated that Mdr1a was function-ally inactive in the blood-brain barrier and intestine in Mdr1a(/) Rats. To identify possible compensatory mecha-nisms in Mdr1a(/) Rats, the expression levels of drug-me-tabolizing enzyme and transporter-related genes were com-pared in brain, liver, kidney, and intestine of male and female Mdr1a(/) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(/) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(/) Rat will be a valuable tool for central nervous sys-tem drug target validation and determining the role of P-gp in drug absorption and disposition
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases.
Molecular pharmacology, 2011Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, Sarah Beth Horwitz, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, John R. StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Pharmacokinetic studies with the Mdr1a P-gp substRates loperamide, indinavir, and talinolol indicated that Mdr1a was functionally inactive in the blood-brain barrier and intestine in Mdr1a(-/-) Rats. To identify possible compensatory mechanisms in Mdr1a(-/-) Rats, the expression levels of drug-metabolizing enzyme and transporter-related genes were compared in brain, liver, kidney, and intestine of male and female Mdr1a(-/-) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(-/-) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(-/-) Rat will be a valuable tool for central nervous system drug target validation and determining the role of P-gp in drug absorption and disposition.
Rachel Ortiga - One of the best experts on this subject based on the ideXlab platform.
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases. Mol Pharmacol 81:220–227
2012Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, Sarah Horwitz, John StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Phar-macokinetic studies with the Mdr1a P-gp substRates lopera-mide, indinavir, and talinolol indicated that Mdr1a was function-ally inactive in the blood-brain barrier and intestine in Mdr1a(/) Rats. To identify possible compensatory mecha-nisms in Mdr1a(/) Rats, the expression levels of drug-me-tabolizing enzyme and transporter-related genes were com-pared in brain, liver, kidney, and intestine of male and female Mdr1a(/) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(/) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(/) Rat will be a valuable tool for central nervous sys-tem drug target validation and determining the role of P-gp in drug absorption and disposition
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases.
Molecular pharmacology, 2011Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, Sarah Beth Horwitz, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, John R. StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Pharmacokinetic studies with the Mdr1a P-gp substRates loperamide, indinavir, and talinolol indicated that Mdr1a was functionally inactive in the blood-brain barrier and intestine in Mdr1a(-/-) Rats. To identify possible compensatory mechanisms in Mdr1a(-/-) Rats, the expression levels of drug-metabolizing enzyme and transporter-related genes were compared in brain, liver, kidney, and intestine of male and female Mdr1a(-/-) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(-/-) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(-/-) Rat will be a valuable tool for central nervous system drug target validation and determining the role of P-gp in drug absorption and disposition.
Harmony Lederman - One of the best experts on this subject based on the ideXlab platform.
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases. Mol Pharmacol 81:220–227
2012Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, Sarah Horwitz, John StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Phar-macokinetic studies with the Mdr1a P-gp substRates lopera-mide, indinavir, and talinolol indicated that Mdr1a was function-ally inactive in the blood-brain barrier and intestine in Mdr1a(/) Rats. To identify possible compensatory mecha-nisms in Mdr1a(/) Rats, the expression levels of drug-me-tabolizing enzyme and transporter-related genes were com-pared in brain, liver, kidney, and intestine of male and female Mdr1a(/) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(/) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(/) Rat will be a valuable tool for central nervous sys-tem drug target validation and determining the role of P-gp in drug absorption and disposition
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases.
Molecular pharmacology, 2011Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, Sarah Beth Horwitz, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, John R. StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Pharmacokinetic studies with the Mdr1a P-gp substRates loperamide, indinavir, and talinolol indicated that Mdr1a was functionally inactive in the blood-brain barrier and intestine in Mdr1a(-/-) Rats. To identify possible compensatory mechanisms in Mdr1a(-/-) Rats, the expression levels of drug-metabolizing enzyme and transporter-related genes were compared in brain, liver, kidney, and intestine of male and female Mdr1a(-/-) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(-/-) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(-/-) Rat will be a valuable tool for central nervous system drug target validation and determining the role of P-gp in drug absorption and disposition.
Lei Zhu - One of the best experts on this subject based on the ideXlab platform.
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases. Mol Pharmacol 81:220–227
2012Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, Sarah Horwitz, John StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Phar-macokinetic studies with the Mdr1a P-gp substRates lopera-mide, indinavir, and talinolol indicated that Mdr1a was function-ally inactive in the blood-brain barrier and intestine in Mdr1a(/) Rats. To identify possible compensatory mecha-nisms in Mdr1a(/) Rats, the expression levels of drug-me-tabolizing enzyme and transporter-related genes were com-pared in brain, liver, kidney, and intestine of male and female Mdr1a(/) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(/) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(/) Rat will be a valuable tool for central nervous sys-tem drug target validation and determining the role of P-gp in drug absorption and disposition
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Characterization of multidrug resistance 1a/P-glycoprotein knockout Rats geneRated by zinc finger nucleases.
Molecular pharmacology, 2011Co-Authors: Xiaoyan Chu, Zuo Zhang, Jocelyn Yabut, Sarah Beth Horwitz, John Levorse, Lei Zhu, Harmony Lederman, Rachel Ortiga, John R. StraussAbstract:The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the Rat genome. The ability to manipulate the Rat genome has great promise to augment the utility of Rats for biological and pharmacological studies. A Wistar Hannover Rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was geneRated using a Rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout Rat. Pharmacokinetic studies with the Mdr1a P-gp substRates loperamide, indinavir, and talinolol indicated that Mdr1a was functionally inactive in the blood-brain barrier and intestine in Mdr1a(-/-) Rats. To identify possible compensatory mechanisms in Mdr1a(-/-) Rats, the expression levels of drug-metabolizing enzyme and transporter-related genes were compared in brain, liver, kidney, and intestine of male and female Mdr1a(-/-) and control Rats. In general, alteRations in gene expression of these genes in Mdr1a(-/-) Rats seemed to be modest, with more changes in female than in male Rats. Taken together, our studies demonstRate that the ZFN-geneRated Mdr1a(-/-) Rat will be a valuable tool for central nervous system drug target validation and determining the role of P-gp in drug absorption and disposition.
