International Mammalian Genome Society

E40 Hypothalamic Cocaine- and Amphetamine-Regulated Transcript (CART) and Serum Leptin Levels are Reduced in the Anorectic anx/anx Mouse

Johansen, J.¹, Broberger, C.², Lavebratt, C.¹, Johansson C.¹, Kuhar, M.³, Hökfelt, T.², Schalling. M¹. ¹Neurogenetics Unit, Department of Molecular Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden; ²Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden; ³Yerkes Regional Primate Center, Emory University, Atlanta, GA 30329, USA

Cocaine and amphetamine regulated transcript (CART) is expressed in the hypothalamus and regulated by leptin. Putative peptides encoded by CART act as potent satiety factors when administered centrally. CART is strongly downregulated in the lateral hypothalamic area and arcuate nucleus in animal models of obesity with disrupted leptin signaling. We have used in situ hybridization and immunohistochemistry to study mice homozygous for the anorexia (anx) mutation which are characterized by a much reduced food intake and early death. anx/anx mice had significantly decreased levels of CART mRNA in the arcuate nucleus. Moreover, serum leptin levels were significantly lower in anx/anx mice compared to normal littermates. The decrease in the anorexic agents leptin and CART may reflect a compensatory downregulation in response to the energy-deprived state of anx/anx mice. Alternatively, the reduced number of arcuate cells with detectable CART levels may be a manifestation of a degenerative process in the hypothalamus of these animals.