Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization
Somatostatin receptor subtype 4 (SST<sub>4</sub>) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST<sub>4<...
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doaj-985786a67a9b4067ac1cffba5c558e2a2021-04-04T23:01:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01223758375810.3390/ijms22073758Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern CharacterizationBalázs Nemes0Kata Bölcskei1Angéla Kecskés2Viktória Kormos3Balázs Gaszner4Timea Aczél5Dániel Hegedüs6Erika Pintér7Zsuzsanna Helyes8Zoltán Sándor9Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryResearch Group for Mood Disorders, Department of Anatomy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryResearch Group for Mood Disorders, Department of Anatomy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, HungarySomatostatin receptor subtype 4 (SST<sub>4</sub>) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST<sub>4</sub> receptor expression and function between humans and mice, we generated an SST<sub>4</sub> humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the <i>hSSTR4</i> and reporter gene construct driven by the <i>hSSTR4</i> regulatory elements were created. The vector was randomly inserted in <i>Sstr4</i>-deficient mice. <i>hSSTR4</i> expression was detected by bioluminescent in vivo imaging of the luciferase reporter predominantly in the brain. RT-qPCR confirmed the expression of the human gene in the brain and various peripheral tissues consistent with the in vivo imaging. RNAscope in situ hybridization revealed the presence of <i>hSSTR4</i> transcripts in glutamatergic excitatory neurons in the CA1 and CA2 regions of the hippocampus; in the GABAergic interneurons in the granular layer of the olfactory bulb and in both types of neurons in the primary somatosensory cortex, piriform cortex, prelimbic cortex and amygdala. This novel SST<sub>4</sub> humanized mouse line might enable us to investigate the differences of human and mouse SST<sub>4</sub> receptor expression and function and assess the effects of SST<sub>4</sub> receptor agonist drug candidates.https://www.mdpi.com/1422-0067/22/7/3758somatostatin<i>Sstr4</i> KO mice<i>SSTR4</i> humanized micePiggyBac (PB) transposon vectorligation-mediated PCRRNAscope in situ hybridization |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Balázs Nemes Kata Bölcskei Angéla Kecskés Viktória Kormos Balázs Gaszner Timea Aczél Dániel Hegedüs Erika Pintér Zsuzsanna Helyes Zoltán Sándor |
spellingShingle |
Balázs Nemes Kata Bölcskei Angéla Kecskés Viktória Kormos Balázs Gaszner Timea Aczél Dániel Hegedüs Erika Pintér Zsuzsanna Helyes Zoltán Sándor Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization International Journal of Molecular Sciences somatostatin <i>Sstr4</i> KO mice <i>SSTR4</i> humanized mice PiggyBac (PB) transposon vector ligation-mediated PCR RNAscope in situ hybridization |
author_facet |
Balázs Nemes Kata Bölcskei Angéla Kecskés Viktória Kormos Balázs Gaszner Timea Aczél Dániel Hegedüs Erika Pintér Zsuzsanna Helyes Zoltán Sándor |
author_sort |
Balázs Nemes |
title |
Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization |
title_short |
Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization |
title_full |
Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization |
title_fullStr |
Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization |
title_full_unstemmed |
Human Somatostatin SST<sub>4</sub> Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization |
title_sort |
human somatostatin sst<sub>4</sub> receptor transgenic mice: construction and brain expression pattern characterization |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
Somatostatin receptor subtype 4 (SST<sub>4</sub>) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST<sub>4</sub> receptor expression and function between humans and mice, we generated an SST<sub>4</sub> humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the <i>hSSTR4</i> and reporter gene construct driven by the <i>hSSTR4</i> regulatory elements were created. The vector was randomly inserted in <i>Sstr4</i>-deficient mice. <i>hSSTR4</i> expression was detected by bioluminescent in vivo imaging of the luciferase reporter predominantly in the brain. RT-qPCR confirmed the expression of the human gene in the brain and various peripheral tissues consistent with the in vivo imaging. RNAscope in situ hybridization revealed the presence of <i>hSSTR4</i> transcripts in glutamatergic excitatory neurons in the CA1 and CA2 regions of the hippocampus; in the GABAergic interneurons in the granular layer of the olfactory bulb and in both types of neurons in the primary somatosensory cortex, piriform cortex, prelimbic cortex and amygdala. This novel SST<sub>4</sub> humanized mouse line might enable us to investigate the differences of human and mouse SST<sub>4</sub> receptor expression and function and assess the effects of SST<sub>4</sub> receptor agonist drug candidates. |
topic |
somatostatin <i>Sstr4</i> KO mice <i>SSTR4</i> humanized mice PiggyBac (PB) transposon vector ligation-mediated PCR RNAscope in situ hybridization |
url |
https://www.mdpi.com/1422-0067/22/7/3758 |
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