Abstract
BackgroundThe 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.ResultsThrough 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.ConclusionTogether, these data support a role for Scg5 in the modulation of body weight.
Highlights
The identification of novel genes is critical to understanding the molecular basis of body weight
BMC Genetics 2008, 9:34 http://www.biomedcentral.com/1471-2156/9/34 we have developed a number of genomic resources with the goal of discerning the molecular basis of chromosome 2 quantitative trait loci (QTL) segregating between the C57BL/6J (B6), C57BL/6Jhg/hg (HG) and CAST/EiJ (CAST) strains [4,5]
Identification of expression QTL overlapping growth and obesity QTL As confirmation of the microarray results, we examined the genetic basis of expression for eleven genes (Cd44, AI451465, Fmn, Scg5, 2310032D16Rik, 3300001M20Rik, Pak7, Actr5, D930001I22Rik, Sdccag33l and Rab22a) identified as differentially expressed from the microarray study (Additional File 1)
Summary
The identification of novel genes is critical to understanding the molecular basis of body weight. BMC Genetics 2008, 9:34 http://www.biomedcentral.com/1471-2156/9/34 we have developed a number of genomic resources with the goal of discerning the molecular basis of chromosome 2 QTL segregating between the C57BL/6J (B6), C57BL/6Jhg/hg (HG) and CAST/EiJ (CAST) strains [4,5]. These include two congenic strains, B6.CAST-(D2Mit329D2Mit457)N(6) (B62D) and HG.CAST-(D2Mit329D2Mit457)N(6) (HG2D), constructed by introgressing an identical congenic donor region, extending from approximately 75 to 180 Mbp, from the CAST strain onto both B6 and HG backgrounds [4]. HG2D mice were not characterized due to reproductive problems, B62D mice displayed significant decreases in growth and obesity traits [4]
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