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

Murtazina, Ramilya Z.; Zhukov, Ilya S.; Korenkova, O.; Popova, Elena; Kuvarzin, Savelii R.; Efimova, Evgeniya V.; Kubarskaya, L. G.; Батоцыренова, Е. Г.; Zolotoverkhaya, Ekaterina A.; Vaganova, Anastasia N.; Apryatin, S A; Alenina, Natalia; Gainetdinov, Raul R.

doi:10.3390/ijms22062942

Cited by 7 publications

(8 citation statements)

References 47 publications

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“…TAAR9-KO rats were generated using CRISPR/Cas9-mediated mutagenesis [ 18 ]. A line of TAAR9-KO rats with single nucleotide deletion (TAAR9-KO delC ) was studied.…”

Section: Methodsmentioning

confidence: 99%

“…A line of TAAR9-KO rats with single nucleotide deletion (TAAR9-KO delC ) was studied. Breeding and genotyping of knockout and wild-type rats were performed as described previously [ 18 ]. Rats were maintained on a 12:12 h light/dark cycle with a light on at 08:00 h and were allowed access to food and water ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, total cholesterol and low-density lipoproteins are decreased in TAAR9-KO animals. The cause of these differences is unknown but may be related to a decreased endogenous cholesterol absorption, biosynthesis, transport, or any other alterations in metabolism [ 18 ]. This receptor can sense amines such as N, N-dimethylcyclohexylamine, N-methylpiperidine, triethylamine, and polyamines, such as cadaverine, putrescine, spermidine, and spermine [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

et al. 2022

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Trace amine-associated receptors (TAAR1-TAAR9) are a family of G-protein-coupled monoaminergic receptors which might have great pharmacological potential. It has now been well established that TAAR1 plays an important role in the central nervous system. Interestingly, deletion of TAAR9 in rats leads to alterations in the periphery. Previously, we found that knockout of TAAR9 in rats (TAAR9-KO rats) decreased low-density lipoprotein cholesterol levels in the blood. TAAR9 was also identified in intestinal tissues, and it is known that it responds to polyamines. To elucidate the role of TAAR9 in the intestinal epithelium, we analyzed TAAR9-co-expressed gene clusters in public data for cecum samples. As identified by gene ontology enrichment analysis, in the intestine, TAAR9 is co-expressed with genes involved in intestinal mucosa homeostasis and function, including cell organization, differentiation, and death. Additionally, TAAR9 was co-expressed with genes implicated in dopamine signaling, which may suggest a role for this receptor in the regulation of peripheral dopaminergic transmission. To further investigate how TAAR9 might be involved in colonic mucosal homeostasis, we analyzed the fecal microbiome composition in TAAR9-KO rats and their wild-type littermates. We identified a significant difference in the number of observed taxa between the microbiome of TAAR9-KO and wild-type rats. In TAAR9-KO rats, the gut microbial community became more variable compared with the wild-type rats. Furthermore, it was found that the family Saccharimonadaceae, which is one of the top 10 most abundant families in TAAR9-KO rat feces, is almost completely absent in wild-type animal fecal samples. Taken together, these data indicate a role of TAAR9 in intestinal function.

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“…TAAR9-KO rats were generated using CRISPR/Cas9-mediated mutagenesis [ 18 ]. A line of TAAR9-KO rats with single nucleotide deletion (TAAR9-KO delC ) was studied.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

et al. 2022

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“…In previous studies, we observed only minimal alteration in blood parameters of TAAR1 knockout (TAAR1-KO) mice [ 12 ]. During a similar investigation in TAAR9-KO rats, we found a significant decrease in total and low-density lipoprotein cholesterol levels under conditions of TAAR9 deficiency [ 14 ]. The present study is devoted to the analysis of hematological parameters of TAAR5 knock-out mice.…”

Section: Introductionmentioning

confidence: 91%

Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice

Zhukov

Kubarskaya

Karpova

et al. 2021

IJMS

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Trace amine-associated receptors (TAARs) are a group of G protein-coupled receptors that are expressed in the olfactory epithelium, central nervous system, and periphery. TAAR family generally consists of nine types of receptors (TAAR1-9), which can detect biogenic amines. During the last 5 years, the TAAR5 receptor became one of the most intriguing receptors in this subfamily. Recent studies revealed that TAAR5 is involved not only in sensing socially relevant odors but also in the regulation of dopamine and serotonin transmission, emotional regulation, and adult neurogenesis by providing significant input from the olfactory system to the limbic brain areas. Such results indicate that future antagonistic TAAR5-based therapies may have high pharmacological potential in the field of neuropsychiatric disorders. TAAR5 is known to be expressed in leucocytes as well. To evaluate potential hematological side effects of such future treatments we analyzed several hematological parameters in mice lacking TAAR5. In these mutants, we observed minor but significant changes in the osmotic fragility test of erythrocytes and hematocrit levels. At the same time, analysis of other parameters including complete blood count and reticulocyte levels showed no significant alterations in TAAR5 knockout mice. Thus, TAAR5 gene knockout leads to minor negative changes in the erythropoiesis or eryptosis processes, and further research in that field is needed. The impact of TAAR5 deficiency on other hematological parameters seems minimal. Such negative, albeit minor, effects of TAAR5 deficiency should be taken into account during future TAAR5-based therapy development.

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“…It was found that deletion of the TAAR5 receptor gene leads to erythrocyte fragility changes [ 53 ]. Furthermore, TAAR9 knockout rats demonstrated decreased low-density lipoprotein cholesterol levels in comparison to control rats [ 54 ]. However, when biochemical and hematological parameters were analyzed in TAAR1 knockout (TAAR1-KO) mice, only the creatine kinase levels were found to be minimally changed in TAAR1-KO male mice [ 55 ].…”

Section: Introductionmentioning

confidence: 99%

Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet

Apryatin

Zhukov

Zolotoverkhaya³

et al. 2023

Neurology International

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Trace amines and their receptors are a family of G protein-coupled receptors widely distributed in the central nervous system and periphery. The trace amine-associated receptor 1 (TAAR1) plays a significant role as a therapeutic target for schizophrenia, depression, diabetes, and obesity. In this study, TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. The consumption of a high-fructose diet may be due to the influence on the metabolism processes by dopamine in the brain, neuromotor function, and level of anxiety of TAAR1 knockout mice. During a comparative analysis of behavioral, biochemical, and morphological parameters, significant differences were found between liver and biochemical parameters, the regulation of protein metabolism (AST/ALT ratio, creatine kinase activity, urea), and alterations in behavior. An elevated plus maze analysis showed the influence of fructose and genetic factors on the level of anxiety. A new marker of the grooming microstructure (depression ratio) was tested, which showed high efficiency as a marker of depression-like behavioral changes and a possible association with dopamine-dependent regulation of protein metabolism. These results confirm a possible association of the TAAR1 gene knockout with an increase in catabolic reaction levels by AST/ALT-dependent and possible dopamine-mediated protein metabolism regulation and depression-like behavior.

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

Cited by 7 publications

References 47 publications

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice

Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet

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