Research article

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

Charles R Farber^1,3 , James Chitwood¹ , Sang-Nam Lee^2,4 , Ricardo A Verdugo¹ , Alma Islas-Trejo¹ , Gonzalo Rincon¹ , Iris Lindberg^2,5 and Juan F Medrano¹

¹Department of Animal Science, University of California, Davis, One Shields Ave., Davis, CA 95616-8521, USA

²Department of Biochemistry and Molecular Biology, Louisiana State University Health, Sciences Center, and Children's Hospital Research Institute, New Orleans, LA 70112-2223, USA

³Department of Medicine, Division of Cardiology, University of, California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095-1679, USA

⁴Research Center for Human Natural Defense System, Yonsei, University College of Medicine, Seoul, 120-752, Korea

⁵Department of Anatomy and Neurobiology, University of, Maryland Medical School, 20 Penn St, Baltimore, MS 21201, USA

author email corresponding author email

BMC Genetics 2008, 9:34doi:10.1186/1471-2156-9-34

Published:	25 April 2008

Abstract

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.