Figure 1.

Generation of a mouse model with selective GHSR expression in AgRP neurons. (A) Schematic diagram of the derivation of AgRP-CreER^T2 mice. The coding sequence of AgRP, found in exons III and IV, was replaced by the coding sequence of a CreER^T2 fusion protein. (B) The desired spatiotemporal expression of cre recombinase in AgRP-CreER^T2 mice was validated by a cross to Rosa26-lox-STOP-lox-tdTomato reporter mice; tdTomato expression (white neurons) was detected selectively in the ARC of tamoxifen (TM)-injected mice but not in vehicle-injected mice (n=3 per group; representative photomicrographs shown; scale bar 100 µm). (C) Ghsr mRNA is expressed in the ARC and VTA of wild-type and wild-type/AgRP-CreER^T2 mice but not in GHSR-null animals as expected, as determined using qRT-PCR; tamoxifen-induced Cre-mediated re-expression of Ghsr mRNA is only observed in the ARC of GHSR-null/AgRP-CreER^T2 mice, but not other regions (mean±SEM, n=4–6 per group).