Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice

• Authors: Ericka M. Boone, University of Illinois; Brian W. Hawks, Emory University; Wei Li, Emory University; Steven Garlow, Emory University
• Journal Title: Brain Research
• Volume: Volume 1194
• Publisher: Elsevier: 12 months | 2008-02-15, Pages 1-7
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.brainres.2007.11.074
• Subjects: Psychology, Behavioral; Health Sciences, Medicine and Surgery; Biology, Neuroscience
• Keywords: Science & Technology; Life Sciences & Biomedicine; Neurosciences; Neurosciences & Neurology; cocaine and amphetamine-regulated transcript; BxD; recombinant inbred mice; hypothalamus; quantitative trait locus; RT-PGR; QUANTITATIVE-TRAIT LOCI; VENTRAL MIDBRAIN; PEPTIDE; EXPRESSION; LOCOMOTOR; PROMOTER; DOPAMINE; COLOCALIZATION; IDENTIFICATION; DISSECTION

Abstract

Cocaine and Amphetamine-Regulated Transcript (CART) peptides are implicated in a wide range of behaviors including in the reinforcing properties of psychostimulants, feeding and energy balance and stress and anxiety responses. We conducted a complex trait analysis to examine natural variation in the regulation of CART transcript abundance (CARTta) in the hypothalamus. CART transcript abundance was measured in total hypothalamic RNA from 26 BxD recombinant inbred (RI) mouse strains and in the C57BL/6 (B6) and DBA/2J (D2) progenitor strains. The strain distribution pattern for CARTta was continuous across the RI panel, which is consistent with this being a quantitative trait. Marker regression and interval mapping revealed significant quantitative trait loci (QTL) on mouse chromosome 4 (around 58.2 cM) and chromosome 11 (between 20-36 cM) that influence CARTta and account for 31% of the between strain variance in this phenotype. There are numerous candidate genes and QTL in these chromosomal regions that may indicate shared genetic regulation between CART expression and other neurobiological processes referable to known actions of this neuropeptide.