| First Author | Meng F | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 13 | Pages | 3645-50 |
| PubMed ID | 26976589 | Mgi Jnum | J:232044 |
| Mgi Id | MGI:5775844 | Doi | 10.1073/pnas.1602049113 |
| Citation | Meng F, et al. (2016) New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism. Proc Natl Acad Sci U S A 113(13):3645-50 |
| abstractText | Currently available inducibleCre/loxPsystems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed fromnsCretransgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes. |
