TY - JOUR

T1 - Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels

AU - Муртазина, Рамиля Зуфаровна

AU - Жуков, Илья Сергеевич

AU - Коренькова, Ольга Михайловна

AU - Попова, Елена

AU - Куварзин, Савелий Ростиславович

AU - Ефимова, Евгения Викторовна

AU - Кубарская, Лариса

AU - Батоцыренова, Екатерина

AU - Золотоверхая, Екатерина

AU - Ваганова, Анастасия Николаевна

AU - Апрятин, Сергей Алексеевич

AU - Аленина, Наталья Владимировна

AU - Гайнетдинов, Рауль Радикович

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/3/2

Y1 - 2021/3/2

N2 - 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.

AB - 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.

KW - Animal knockout model

KW - Cholesterol

KW - GPCR

KW - Low-density lipoprotein

KW - TAAR

KW - TAAR9

KW - Trace amine-associated receptor

KW - Trace amines

KW - Humans

KW - Erythrocytes/metabolism

KW - Rats

KW - Gene Knockout Techniques

KW - Osmotic Fragility/genetics

KW - Central Nervous System/metabolism

KW - Receptors, G-Protein-Coupled/genetics

KW - Animals

KW - Cholesterol/blood

KW - CRISPR-Cas Systems

KW - Ligands

KW - Atherosclerosis/blood

KW - Disease Models, Animal

KW - trace amines

KW - animal knockout model

KW - cholesterol

KW - low-density lipoprotein

KW - trace amine-associated receptor

UR - http://www.scopus.com/inward/record.url?scp=85102354126&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/d12316d9-7115-373e-ab3c-e658f4aa8abb/

U2 - 10.3390/ijms22062942

DO - 10.3390/ijms22062942

M3 - Article

C2 - 33799339

VL - 22

SP - 1

EP - 15

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 6

M1 - 2942

ER -