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Background  The identification of novel genes is critical to understanding the molecular basis of body weight. Towards this goal, we have identified secretogranin V ( Scg5 ; also referred to as  Sgne1 ), as a candidate gene for growth traits.    Results  Through a combination of DNA microarray analysis and quantitative PCR we identified a strong expression quantitative trait locus (eQTL) regulating  Scg5  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  Scg5  expression was negatively correlated with body weight in two of the F2 intercrosses. Analysis of haplotype blocks and genomic sequencing of  Scg5  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  Scg5  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.    Conclusion  Together, these data support a role for  Scg5  in the modulation of body weight.

Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice