Development and Characterization of a -Flp Mouse Model.

The use of genetically engineered tools, including combinations of Cre-LoxP and Flp-FRT systems, enable the interrogation of complex biology. Steroidogenic factor-1 (SF-1) is expressed in the ventromedial hypothalamic nucleus (VMH). Development of genetic tools, such as mice expressing Flp recombinase (Flp) in SF-1 neurons ( -Flp), will be useful for future studies that unravel the complex physiology regulated by the VMH. Here, we developed and characterized -Flp mice and demonstrated its utility. Flp sequence was inserted into locus with P2A. This insertion did not affect mRNA expression levels and -Flp mice do not have any visible phenotypes. They are fertile and metabolically comparable to wild-type littermate mice. Optogenetic stimulation using adeno-associated virus (AAV)-bearing Flp-dependent channelrhodopsin-2 (ChR2) increased blood glucose and skeletal muscle PGC-1α in -Flp mice. This was similar to SF-1 neuronal activation using -BAC-Cre and AAV-bearing Cre-dependent ChR2. Finally, we generated -Flp mice that lack ( ) only in skeletal muscle with a combination of Cre/LoxP technology ( -Flp::SKM ). Optogenetic stimulation of SF-1 neurons failed to increase skeletal muscle PGC-1α in -Flp::SKM mice, suggesting that in skeletal muscle is for augmented skeletal muscle PGC-1α by SF-1 neuronal activation. Our data demonstrate that -Flp mice are useful for interrogating complex physiology.