Human Somatostatin SST4 Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization

Nemes, Balázs and Bölcskei, Kata and Kecskés, Angéla and Kormos, Viktória and Gaszner, Balázs and Aczél, Timea and Pintér, Erika and Helyes, Zsuzsanna and Sándor, Zoltán (2021) Human Somatostatin SST4 Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (7). ISSN 1661-6596


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Somatostatin receptor subtype 4 (SST4) 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 SST4 receptor expression and function between humans and mice, we generated an SST4 humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the hSSTR4 and reporter gene construct driven by the hSSTR4 regulatory elements were created. The vector was randomly inserted in Sstr4-deficient mice. hSSTR4 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 hSSTR4 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 SST4 humanized mouse line might enable us to investigate the differences of human and mouse SST4 receptor expression and function and assess the effects of SST4 receptor agonist drug candidates.

Item Type: Article
Uncontrolled Keywords: SOMATOSTATIN; RNAscope in situ hybridization; Sstr4 KO mice; SSTR4 humanized mice; PiggyBac (PB) transposon vector; ligation-mediated PCR;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Depositing User: MTMT SWORD
Date Deposited: 27 Sep 2021 14:25
Last Modified: 27 Sep 2021 14:25

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