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Publication : A critical view of the use of genetic tools to unveil neural circuits: the case of leptin action in reproduction.

First Author  Elias CF Year  2014
Journal  Am J Physiol Regul Integr Comp Physiol Volume  306
Issue  1 Pages  R1-9
PubMed ID  24196667 Mgi Jnum  J:208096
Mgi Id  MGI:5560885 Doi  10.1152/ajpregu.00444.2013
Citation  Elias CF (2014) A critical view of the use of genetic tools to unveil neural circuits: the case of leptin action in reproduction. Am J Physiol Regul Integr Comp Physiol 306(1):R1-9
abstractText  The remarkable development and refinement of the Cre-loxP system coupled with the nonstop production of new mouse models and virus vectors have impelled the growth of various fields of investigation. In this article, I will discuss the data collected using these genetic tools in our area of interest, giving specific emphasis to the identification of the neuronal populations that relay leptin action in reproductive physiology. A series of mouse models that allow manipulation of the leptin receptor gene have been generated. Of those, I will discuss the use of two models of leptin receptor gene reexpression (LepR(neo/neo) and LepR(loxTB/loxTB)) and one model of leptin signaling blockade (LepR(flox/flox)). I will also highlight the differences of using stereotaxic delivery of virus vectors expressing DNA-recombinases (Flp and Cre) and mouse models expressing Cre-recombinase. Our findings indicate that leptin action in the ventral premammillary nucleus is sufficient, but not required, for leptin action in reproduction and that leptin action in Kiss1 neurons arises after pubertal maturation; therefore, direct leptin signaling in Kiss1 neurons is neither required nor sufficient for the permissive action of leptin in pubertal development. It also became evident that the full action of leptin in the reproductive neuroendocrine axis requires the engagement of an integrated circuitry, yet to be fully unveiled.
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