Summary: | <p>Abstract</p> <p>Background</p> <p>The identification of novel genes is critical to understanding the molecular basis of body weight. Towards this goal, we have identified secretogranin V (<it>Scg5</it>; also referred to as <it>Sgne1</it>), as a candidate gene for growth traits.</p> <p>Results</p> <p>Through a combination of DNA microarray analysis and quantitative PCR we identified a strong expression quantitative trait locus (eQTL) regulating <it>Scg5 </it>expression in two mouse chromosome 2 congenic strains and three additional F2 intercrosses. More importantly, the eQTL was coincident with a body weight QTL in congenic mice and <it>Scg5 </it>expression was negatively correlated with body weight in two of the F2 intercrosses. Analysis of haplotype blocks and genomic sequencing of <it>Scg5 </it>in high (C3H/HeJ, DBA/2J, BALB/cByJ, CAST/EiJ) and low (C57BL/6J) expressing strains revealed mutations unique to C57BL/6J and possibly responsible for the difference in mRNA abundance. To evaluate the functional consequence of <it>Scg5 </it>overexpression we measured the pituitary levels of 7B2 protein and PCSK2 activity and found both to be increased. In spite of this increase, the level of pituitary α-MSH, a PCSK2 processing product, was unaltered.</p> <p>Conclusion</p> <p>Together, these data support a role for <it>Scg5 </it>in the modulation of body weight.</p>
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