Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels
In the last two decades, interest has grown significantly in the investigation of the role of trace amines and their receptors in mammalian physiology and pathology. Trace amine-associated receptor 9 (TAAR9) is one of the least studied members of this receptor family with unidentified endogenous lig...
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2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ramilya Z. Murtazina Ilya S. Zhukov Olga M. Korenkova Elena A. Popova Savelii R. Kuvarzin Evgeniya V. Efimova Larisa G. Kubarskaya Ekaterina G. Batotsyrenova Ekaterina A. Zolotoverkhaya Anastasia N. Vaganova Sergey A. Apryatin Natalia V. Alenina Raul R. Gainetdinov |
| author_facet | Ramilya Z. Murtazina Ilya S. Zhukov Olga M. Korenkova Elena A. Popova Savelii R. Kuvarzin Evgeniya V. Efimova Larisa G. Kubarskaya Ekaterina G. Batotsyrenova Ekaterina A. Zolotoverkhaya Anastasia N. Vaganova Sergey A. Apryatin Natalia V. Alenina Raul R. Gainetdinov |
| author_sort | Ramilya Z. Murtazina |
| collection | DOAJ |
| description | In the last two decades, interest has grown significantly in the investigation of the role of trace amines and their receptors in mammalian physiology and pathology. Trace amine-associated receptor 9 (TAAR9) is one of the least studied members of this receptor family with unidentified endogenous ligands and an unknown role in the central nervous system and periphery. In this study, we generated two new TAAR9 knockout (TAAR9-KO) rat strains by CRISPR-Cas9 technology as in vivo models to evaluate the role of TAAR9 in mammalian physiology. In these mutant rats, we performed a comparative analysis of a number of hematological and biochemical parameters in the blood. Particularly, we carried out a complete blood count, erythrocyte osmotic fragility test, and screening of a panel of basic biochemical parameters. No significant alterations in any of the hematological and most biochemical parameters were found between mutant and WT rats. However, biochemical studies revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of both strains of TAAR9-KO rats. Such role of TAAR9 in cholesterol regulation not only brings a new understanding of mechanisms and biological pathways of lipid exchange but also provides a new potential drug target for disorders involving cholesterol-related pathology, such as atherosclerosis. |
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| language | English |
| last_indexed | 2024-03-10T13:15:32Z |
| publishDate | 2021-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-855ed6ed5afa4ed6a8c4c7ad397a956e2023-11-21T10:25:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226294210.3390/ijms22062942Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol LevelsRamilya Z. Murtazina0Ilya S. Zhukov1Olga M. Korenkova2Elena A. Popova3Savelii R. Kuvarzin4Evgeniya V. Efimova5Larisa G. Kubarskaya6Ekaterina G. Batotsyrenova7Ekaterina A. Zolotoverkhaya8Anastasia N. Vaganova9Sergey A. Apryatin10Natalia V. Alenina11Raul R. Gainetdinov12Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Roessle-str. 10, 13125 Berlin, GermanyInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Toxicology of Federal Medical-Biological Agency, Bekhtereva str. 1, 192019 Saint Petersburg, RussiaInstitute of Toxicology of Federal Medical-Biological Agency, Bekhtereva str. 1, 192019 Saint Petersburg, RussiaInstitute of Toxicology of Federal Medical-Biological Agency, Bekhtereva str. 1, 192019 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7-9, 199034 Saint Petersburg, RussiaIn the last two decades, interest has grown significantly in the investigation of the role of trace amines and their receptors in mammalian physiology and pathology. Trace amine-associated receptor 9 (TAAR9) is one of the least studied members of this receptor family with unidentified endogenous ligands and an unknown role in the central nervous system and periphery. In this study, we generated two new TAAR9 knockout (TAAR9-KO) rat strains by CRISPR-Cas9 technology as in vivo models to evaluate the role of TAAR9 in mammalian physiology. In these mutant rats, we performed a comparative analysis of a number of hematological and biochemical parameters in the blood. Particularly, we carried out a complete blood count, erythrocyte osmotic fragility test, and screening of a panel of basic biochemical parameters. No significant alterations in any of the hematological and most biochemical parameters were found between mutant and WT rats. However, biochemical studies revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of both strains of TAAR9-KO rats. Such role of TAAR9 in cholesterol regulation not only brings a new understanding of mechanisms and biological pathways of lipid exchange but also provides a new potential drug target for disorders involving cholesterol-related pathology, such as atherosclerosis.https://www.mdpi.com/1422-0067/22/6/2942trace aminestrace amine-associated receptorTAARTAAR9low-density lipoproteincholesterol |
| spellingShingle | Ramilya Z. Murtazina Ilya S. Zhukov Olga M. Korenkova Elena A. Popova Savelii R. Kuvarzin Evgeniya V. Efimova Larisa G. Kubarskaya Ekaterina G. Batotsyrenova Ekaterina A. Zolotoverkhaya Anastasia N. Vaganova Sergey A. Apryatin Natalia V. Alenina Raul R. Gainetdinov Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels International Journal of Molecular Sciences trace amines trace amine-associated receptor TAAR TAAR9 low-density lipoprotein cholesterol |
| title | Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels |
| title_full | Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels |
| title_fullStr | Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels |
| title_full_unstemmed | Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels |
| title_short | Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels |
| title_sort | genetic deletion of trace amine associated receptor 9 taar9 in rats leads to decreased blood cholesterol levels |
| topic | trace amines trace amine-associated receptor TAAR TAAR9 low-density lipoprotein cholesterol |
| url | https://www.mdpi.com/1422-0067/22/6/2942 |
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