Somatostatin-IRES-Cre Mice: Between Knockout and Wild-Type?

Area of Science:

• Neuroscience
• Genetics
• Endocrinology

Background:

• Somatostatin (SOM) is a crucial neuropeptide in the brain, and SOM-IRES-Cre (SOM-cre) mouse models are vital for studying SOM-containing neurons.
• While knock-in strategies enhance Cre-Lox system accuracy, the insertion of Cre constructs can inadvertently alter physiological functions.

Purpose of the Study:

• To investigate the physiological impact of Cre transgene insertion in the 3'UTR of the somatostatin gene in SOM-cre mice.
• To evaluate the neuroendocrine consequences of altered SOM levels in this mouse model.

Main Methods:

• Analysis of endogenous SOM levels in various brain regions of SOM-cre mice.
• Assessment of neuroendocrine responses, including corticosterone levels and growth hormone secretion patterns.
• Examination of sexually dimorphic gene expression in the liver.

Main Results:

• Cre transgene insertion in the 3'UTR of the somatostatin gene caused massive depletion of endogenous SOM across all tested brain regions.
• Neuroendocrine responses mimicked those of Somatostatin Knockout (SST KO) mice, with increased corticosterone and altered growth hormone secretion.
• Significant changes in sexually dimorphic liver gene expression (serpina1, Cyp2b9, Cyp2a4, Cyp2d9, Cyp7b1) were observed.

Conclusions:

• The Cre construct insertion in the SOM-cre mouse strain significantly affects endogenous SOM levels and related neuroendocrine functions.
• These findings underscore the importance of evaluating Cre transgenesis effects in genetically modified mouse models.
• The SOM-cre strain, despite its limitations, may serve as a valuable tool for studying conditions with moderate to low SOM levels, such as neurological and psychiatric disorders.