Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases
Nitric oxide (NO) is produced in almost all tissues and organs, exerting multiple biological actions under both physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS): neuronal, inducible, and endothelial NOSs. Due to the substantial compensator...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319343889 |
| _version_ | 1818854392578703360 |
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| author | Masato Tsutsui Hiroaki Shimokawa Tsuyoshi Morishita Yasuhide Nakashima Nobuyuki Yanagihara |
| author_facet | Masato Tsutsui Hiroaki Shimokawa Tsuyoshi Morishita Yasuhide Nakashima Nobuyuki Yanagihara |
| author_sort | Masato Tsutsui |
| collection | DOAJ |
| description | Nitric oxide (NO) is produced in almost all tissues and organs, exerting multiple biological actions under both physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS): neuronal, inducible, and endothelial NOSs. Due to the substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. To address this point, we have successfully developed mice in which all three NOS genes are completely disrupted. NOS expression and activities were totally absent in the triply n/i/eNOS−/− mice before and after treatment with lipopolysaccharide. While the triply n/i/eNOS−/− mice were viable, their survival and fertility rates were markedly reduced as compared with wild-type mice. The phenotypes of those mice that we first noticed were polyuria, polydipsia, and renal unresponsiveness to vasopressin, characteristics consistent with nephrogenic diabetes insipidus. We subsequently observed that in those mice, arteriosclerosis is spontaneously developed with a clustering of cardiovascular risk factors. These results provide the first evidence that the systemic deletion of all three NOSs causes a variety of cardiovascular diseases in mice, demonstrating a critical role of the endogenous NOSs system in maintaining cardiovascular homeostasis. Keywords:: nitric oxide synthase, knockout mouse, cardiovascular disease, nephrogenic diabetes insipidus, metabolic syndrome |
| first_indexed | 2024-12-19T07:51:59Z |
| format | Article |
| id | doaj.art-59b02096d55a44a79a296e2d044f9552 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-19T07:51:59Z |
| publishDate | 2006-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-59b02096d55a44a79a296e2d044f95522022-12-21T20:30:07ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-011022147154Development of Genetically Engineered Mice Lacking All Three Nitric Oxide SynthasesMasato Tsutsui0Hiroaki Shimokawa1Tsuyoshi Morishita2Yasuhide Nakashima3Nobuyuki Yanagihara4Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan; Corresponding author. mt2498@med.uoeh-u.ac.jpDepartment of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, JapanSecond Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, JapanSecond Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, JapanDepartment of Pharmacology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, JapanNitric oxide (NO) is produced in almost all tissues and organs, exerting multiple biological actions under both physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS): neuronal, inducible, and endothelial NOSs. Due to the substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. To address this point, we have successfully developed mice in which all three NOS genes are completely disrupted. NOS expression and activities were totally absent in the triply n/i/eNOS−/− mice before and after treatment with lipopolysaccharide. While the triply n/i/eNOS−/− mice were viable, their survival and fertility rates were markedly reduced as compared with wild-type mice. The phenotypes of those mice that we first noticed were polyuria, polydipsia, and renal unresponsiveness to vasopressin, characteristics consistent with nephrogenic diabetes insipidus. We subsequently observed that in those mice, arteriosclerosis is spontaneously developed with a clustering of cardiovascular risk factors. These results provide the first evidence that the systemic deletion of all three NOSs causes a variety of cardiovascular diseases in mice, demonstrating a critical role of the endogenous NOSs system in maintaining cardiovascular homeostasis. Keywords:: nitric oxide synthase, knockout mouse, cardiovascular disease, nephrogenic diabetes insipidus, metabolic syndromehttp://www.sciencedirect.com/science/article/pii/S1347861319343889 |
| spellingShingle | Masato Tsutsui Hiroaki Shimokawa Tsuyoshi Morishita Yasuhide Nakashima Nobuyuki Yanagihara Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases Journal of Pharmacological Sciences |
| title | Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases |
| title_full | Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases |
| title_fullStr | Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases |
| title_full_unstemmed | Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases |
| title_short | Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases |
| title_sort | development of genetically engineered mice lacking all three nitric oxide synthases |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319343889 |
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