Minimal Age-Related Alterations in Behavioral and Hematological Parameters in Trace Amine-Associated Receptor 1 (TAAR1) Knockout Mice

Zhukov, Ilya S.; Kubarskaya, L. G.; Tissen, Ilia Yu.; Kozlova, Alena A.; Dagayev, S. G.; Kashuro, V. A.; Власова, О. Л.; Sinitca, E. L.; Karpova, I. V.; Gainetdinov, Raul R.

doi:10.1007/s10571-019-00721-4

Cited by 8 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent publication by Zhukov et al [29] on adult and middleaged 45 weeks old Taar1 knockout mice claimed minimal changes in hematological readouts and behavior while no relevant alterations of free T4 and free T3 serum concentrations were reported. These hormone values might not represent adequate analysis, as a platform designed to determine human free TH serum concentration was used for the murine sera, which have quite different blood composition and TH distributor proteins, thereby preventing precise measurement of free TH concentrations.…”

Section: Effects Of 3-t1am On Processes Involved In Thyroid Cell Biolmentioning

confidence: 97%

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

Homuth

Lietzow

Schanze

et al. 2020

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

Thyroid hormone metabolites (THM) with few or no iodine substituents such as 3,5-T2, the thyronamines 3-T1AM and T0AM, and their oxidation products, the thyroacetic acids (TA) formed by monoamine oxidases, have recently attracted major interest due to their metabolic actions which are in part distinct from those of the classical thyromimetic hormone T3, the major ligand of T3 receptors. This review compiles and discusses in vitro effects of 3,5-T2, TAM and TA reported for thyrocytes, pancreatic islets and hepatocytes as well as findings from in vivo studies in mouse models after single or repeated administration of pharmacological doses of these agents. Comparison of the 3,5-T2 effects on the transcriptome with not yet published proteome data in livers of obese mice on high fat diet indicate a distinct anti-steatotic effect of this THM. Furthermore, uptake, metabolism, and cellular actions via various receptors such as trace amine-associated receptors (TAAR), alpha-adrenergic, GPCR and T3 receptors are discussed. Studies on postulated pathways of biosynthesis of 3-T1AM, its effects on the HPT-axis and thyroid gland as well as insulin secretion are reviewed. 3-T1AM also acts on hepatocytes and interferes with TRPM8-dependent signaling in human cell lines related to the eye compartment. Human studies are presented which address potential biosynthesis routes of 3,5-T2 and 3-T1AM from THM precursors, especially T3. The current state of diagnostic analytics of these minor THM in human blood is portrayed comparing and critically discussing the still divergent findings based on classical immunoassay and recently developed liquid-chromatography/mass- spectrometry methods, which allow quantification of the thyronome spectrum from one single small volume serum sample. The clinical perspectives of use and potential abuse of these biologically active THM is addressed.

show abstract

Section: Effects Of 3-t1am On Processes Involved In Thyroid Cell Biolmentioning

confidence: 97%

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

Homuth

Lietzow

Schanze

et al. 2020

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

show abstract

“…WBC ( Figure 5 a–f) and WBC differential ( Figure 5 g) of TAAR9-KO and WT rats were analyzed [ 20 ]. Results of WBC analysis are presented as concentration ( Figure 5 a–f) and leukocyte formula view ( Figure 5 g).…”

Section: Resultsmentioning

confidence: 99%

“…Trunk blood was placed into VACUETTE K3-EDTA tubes (Greiner Bio-One, Kremsmünster, Austria), and stored at +4 °C or room temperature before the experiment (samples were analyzed within 1–3 h after blood collection). After hematological measurement, red blood cells (RBC) of each sample were isolated for osmotic fragility test [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Hematological tests were performed using an automated hematology analyzer ADVIA 2120i (Siemens Healthcare Diagnostics, Eschborn, Germany) as described in [ 20 ]. This flow cytometry-based system uses light scatter, differential white blood cell (WBC) lysis, and myeloperoxidase and oxazine 750 staining to provide a complete blood cell (CBC), a WBC differential, and reticulocyte counts.…”

Section: Methodsmentioning

confidence: 99%

“…While currently there are no reports on TAAR9 knockout animals, it is known that a mouse line with a cluster deletion (TAAR2-9) lacking all TAARs expressed in the olfactory epithelium showed no differences in comparison to WT with regard to fertility, litter size, distribution of genotype, and sex-ratio of pups, but demonstrated significant alterations in sexual behaviors related to the recognition of breeding partners and mate choice [ 19 ]. In this study, we generated two strains of TAAR9–KO rats using CRISPR/Cas9-mediated mutagenesis and focused on the analysis of hematological and basic biochemical parameters in the blood of TAAR9-KO rats by applying the protocol that we developed recently for TAAR1 knockout mice [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Murtazina

Zhukov

Korenkova

et al. 2021

IJMS

View full text Add to dashboard Cite

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.

show abstract

Trace Amines and Trace Amine-Associated Receptors: A New Frontier in Cell Signaling

Freyberg

Saavedra

2020

Cell Mol Neurobiol

View full text Add to dashboard Cite

Minimal Age-Related Alterations in Behavioral and Hematological Parameters in Trace Amine-Associated Receptor 1 (TAAR1) Knockout Mice

Cited by 8 publications

References 20 publications

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

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

Trace Amines and Trace Amine-Associated Receptors: A New Frontier in Cell Signaling

Contact Info

Product

Resources

About