Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice

• DOI: 10.1016/j.molmet.2021.101431
• Publication Date: 2021-12-31T03:06:06Z
• Authors: Jason D. Meadows; Joseph A. Breuer; Shanna N. Lavalle; Michael R. Hirsch...; Meera M. Patel; Duong Nguyen; Alyssa Kim; Jessica Cassin; Michael R. Gorman; David K. Welsh; Pamela L. Mellon; Hanne M. Hoffmann
• Keywords: Dwarfism

The increasing prevalence of obesity makes it important to increase the understanding maturation and function neuronal integrators regulators metabolic function. Behavioral, molecular, physiological analyses transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using Synapsincreallele. Conditional deletion homeodomain transcription factor Six3 causes dwarfism weakens circadian wheel-running activity rhythms but increases general at night, improves function, without impacting pubertal onset or fertility males. reduced growth 6-week-old Six3fl/fl:Synapsincre (Six3syn) males correlates increased somatostatin (SS) expression hypothalamus hormone (GH) pituitary. In contrast, 12-week-old Six3syn have GH release, despite an number inhibitory SS periventricular nucleus. is glucose metabolism, muscle bone health. Interestingly, improved tolerance 7, 12, 18 weeks age, which, adulthood, associated % lean mass rates. Further, mineralization a lower mineral density, indicating that levels during early life cause long-term reduction mineralization. Our study points novel role post-proliferative regulate through neuron control release.