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Development and characterization of an Sf-1-Flp mouse model.

Marco Galvan¹, Mina Fujitani¹, Samuel R Heaselgrave¹

¹Center for Hypothalamic Research, Department of Internal Medicine.

|March 4, 2025

Summary

This summary is machine-generated.

New Sf-1-Flp mice enable the study of complex physiology regulated by the ventromedial hypothalamus (VMH). These mice demonstrate that β2-adrenergic receptors in skeletal muscle are crucial for SF-1 neuron-mediated PGC-1α regulation.

Keywords:

Diabetes Glucose metabolism Metabolism Neuroscience

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Area of Science:

Neuroscience
Genetics
Endocrinology

Background:

Genetically engineered tools like Cre-LoxP and Flp-FRT systems are vital for dissecting complex biological processes.
Steroidogenic factor-1 (SF-1) is a key transcription factor expressed in the ventromedial hypothalamic nucleus (VMH), a region controlling complex physiology.
The development of specific genetic tools for SF-1 expressing neurons is essential for advancing research in VMH-regulated functions.

Purpose of the Study:

To develop and characterize novel Flp recombinase expressing mice specifically in SF-1 neurons (Sf-1-Flp mice).
To validate the utility of Sf-1-Flp mice in studying VMH-regulated physiological processes.
To investigate the role of skeletal muscle β2-adrenergic receptors in SF-1 neuron-mediated metabolic regulation.

Main Methods:

Generation of Sf-1-Flp mice by inserting a Flp recombinase sequence into the Sf-1 locus.
Characterization of Sf-1-Flp mice for phenotypes, fertility, and metabolic status compared to wild-type.
Utilized optogenetics with adeno-associated virus (AAV) vectors for neuronal activation and genetic manipulation (Cre/LoxP) to delete specific genes.

Main Results:

Sf-1-Flp mice exhibited normal SF-1 mRNA expression, no visible phenotypes, and were fertile and metabolically comparable to controls.
Optogenetic stimulation of SF-1 neurons in Sf-1-Flp mice increased blood glucose and skeletal muscle PGC-1α, similar to SF-1-BAC-Cre mice.
In Sf-1-Flp mice lacking skeletal muscle β2-adrenergic receptors, SF-1 neuron activation failed to increase skeletal muscle PGC-1α, indicating receptor necessity.

Conclusions:

Sf-1-Flp mice are a valuable genetic tool for investigating complex physiology regulated by SF-1 neurons in the VMH.
SF-1 neuronal activation influences skeletal muscle PGC-1α expression.
Skeletal muscle β2-adrenergic receptors are required for the SF-1 neuron-mediated augmentation of skeletal muscle PGC-1α.