Ž . Brain Research 848 1999 137–140 www.elsevier.comrlocaterbres Interactive report CART: from gene to function 1 Larry D. Adams, Wenhe Gong, Stephanie Dall Vechia, Richard G. Hunter, Michael J. Kuhar ) Yerkes Regional Primate Research Center of Emory UniÕersity, 954 Gatewood Road NE, Atlanta, GA 30329, USA Accepted 30 July 1999 Abstract CART was identified as a novel mRNA regulated by psychostimulant drugs. CART peptides appear to be neurotransmitters involved in a variety of functions such as feeding. The mouse gene has been characterized and localized to Chromosome 13. The processing of CART peptides is evident in Western blotting studies. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Neuropeptide; Cocaine; Feeding 1. Introduction CART peptides are putative neurotransmittersrcotrans- w x mitters in the brain and gut 12 . CART mRNA was first identified as an mRNA that was upregulated in response to wx acute administrations of psychostimulant drugs 4 . The wx mRNA was highly abundant 6 , and widely distributed in w x the brain, gut, adrenal gland and pituitary 4,2 . The predicted protein product of CART mRNA had a leader sequence suggesting its insertion into the secretion pathway as well as pairs of basic amino acids suggesting subsequent post-translational processing into smaller pep- wx w x tides 4 . The identification by Spiess et al. 18 of a fragment of CART protein that began after a pair of basic amino acids suggested that CART protein was, in fact, translated and processed in the brain. Subsequent studies showed that CART peptide immunoreactivity was found in w the same cell groups that contained CART mRNA 8– x 10,16,17,21 , and Western blotting has revealed a multi- plicity of CART peptide fragments throughout the brain, w x gut, adrenal gland, and pituitary gland 13 . Recently, several of these species have been sequenced and the w x results are compatible with known processing patterns 19 . CART protein and peptides have been reported to have Ž . biological activity. Human CART hCART is thought to have some neurotrophic properties, as it promotes neuronal w x development and survival in culture 15 . Also, CART ) Corresponding author. Tel.: q1-404-727-1737; Fax: q1-404-727- 3278; E-mail: mkuhar@rmy.emory.edu 1 Published on the World Wide Web on 10 August 1999. w x peptides inhibit feeding behavior 14,11,20 and have psy- wx chostimulant-like effects on locomotor behavior 7 . This paper reviews some of the more recent findings on the CART gene in the mouse, the multiplicity and process- ing of CART peptides, as well as a brief review of its effects on feeding. 2. The mouse CART gene A baculovirus library of ES129-SVrJ mouse cell ge- nomic clones was screened with a full-length radiolabeled rat CART cDNA probe. Several clones were identified and sequenced, revealing a putative mouse CART gene con- tained in over 2 kB. The gene was identified based on the similarity of sequences with those found in rat and human wx CART cDNAs as well as in the human CART gene 3. Like the human gene, the mouse gene contained a coding region of three exons, a 5 X region containing a consensus tata box, and a 3 X region with poly-A addition site signals Ž . Fig. 1 . A BLAST sequence similarity search was carried out in the gene bank database and four EST mouse cDNAs were found with high homology to the rat and human CART cDNAs respectively. The presence of these four ESTs indicate that the CART gene is translated in the mouse as might be expected. The identification of these ESTs are: A13422575; A1324263; A031207; and W12030. The predicted amino acid sequence of the mouse CART protein is 98% and 96% identical to the rat and human, respectively. In order to determine if the CART protein is w x made and processed in the mouse as it is in the rat 13,19 , 0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01907-1