Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice.
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 alpha-MSH, a PCSK2 processing product, was unaltered.


CONCLUSIONS
Together, these data support a role for Scg5 in the modulation of body weight.
Farber
Charles R
CR
Department of Animal Science, University of California, Davis, One Shields Ave., Davis, CA 95616-8521, USA. cfarber@mednet.ucla.edu
Chitwood
James
J
Lee
Sang-Nam
SN
Verdugo
Ricardo A
RA
Islas-Trejo
Alma
A
Rincon
Gonzalo
G
Lindberg
Iris
I
Medrano
Juan F
JF
D000818:Animals; D001835:Body Weight / Q000235:genetics*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D020297:Mice, Congenic; D051859:Neuroendocrine Secretory Protein 7B2 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D045706:Proprotein Convertase 2 / Q000235:genetics*; D040641:Quantitative Trait Loci; D017422:Sequence Analysis, DNA; D015854:Up-Regulation
D051859:Neuroendocrine Secretory Protein 7B2; D045706:Proprotein Convertase 2