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

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Somatostatin receptor subtype 4 (SST₄) mediates analgesic, antidepressant, and anti-inflammatory effects without endocrine actions.
• SST₄ is a promising target for novel drug development.
• Species-specific differences in SST₄ receptor expression and function pose challenges for preclinical research.

Purpose of the Study:

• To develop a translational animal model for preclinical research by creating an SST₄ humanized mouse line.
• To overcome species differences in SST₄ receptor expression and function between humans and mice.

Main Methods:

• Generated a transposon vector with the human SST₄ (hSSTR4) gene and a reporter gene.
• Randomly inserted the vector into Sstr4-deficient mice.
• Utilized bioluminescent in vivo imaging, RT-qPCR, and RNAscope in situ hybridization to confirm hSSTR4 expression and localization.

Main Results:

• Successfully generated an SST₄ humanized mouse line with hSSTR4 expression confirmed in the brain and peripheral tissues.
• In vivo imaging showed predominant brain expression of hSSTR4.
• In situ hybridization revealed hSSTR4 transcripts in specific neuronal populations within the hippocampus, olfactory bulb, somatosensory cortex, piriform cortex, prelimbic cortex, and amygdala.

Conclusions:

• The novel SST₄ humanized mouse line serves as a valuable translational model.
• This model facilitates investigation into human-specific SST₄ receptor expression and function.
• It enables the assessment of SST₄ receptor agonist drug candidates in a more relevant preclinical setting.