Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  2
• Reference
  J:127206 Chiu S, et al., Identification of positional candidate genes for body weight and adiposity in subcongenic mice. Physiol Genomics. 2007 Sep 19;31(1):75-85
• ID
  MGI:3765920

Genes

Gene	Assay Type
Bsbob	visible phenotype
D2Mit194	PCR amplified length variant
D2Mit311	PCR amplified length variant
Cfap61	reported elsewhere
Snrpb2	reported elsewhere
Pcsk2	reported elsewhere
Polr3f	reported elsewhere
Ovol2	reported elsewhere
Rrbp1	reported elsewhere

Notes

• Experiment
  Previously identified obesity QTL Bsbob (79 cM) on mouse Chromosome 2 was further characterized using subcongenic line analysis. B6.S-(D2Mit194-D2Mit311) carries SPRET/EiJ-derived DNA between 81.4 cM and 83.1 cM on a C57BL/6J genetic background. This line exhibits a lean phenotype and was subdivided into 5 overlapping genetic regions. Fine map and phenotype analysis were performed using 16- to 18-week old male F2 animals derived from each subcongenic line crossed to B6.129P2-Lipc^tm1Unc/J.
  
  The Bsbob critical region was refined to a 7 Mb interval between D2Bsb36 (140 Mb) and UWmicro22 (147 Mb). Animals with SPRET/EiJ-derived alleles at this interval display significantly decreased femoral, epididymal, and mesenteric white adipose tissue mass, and decreased adiposity index with a dominant mode of inheritance. This allele also appears to decrease food intake while increasing food efficiency, and confers decreased body length compared to the C57BL/6J allele.
  
  Candidate genes were identified via differential gene expression in adipose tissue of SPRET/EiJ and C57BL/6J animals. 4930529M08Rik (143.72 Mb) is upregulate in SPRET/EiJ while Snrpb2 (142.75 Mb), Pcsk2 (143.24 Mb), Polr3f (144.22 Mb), Ovol2 (144 Mb), and Rrbp1 (143.64 cM) are downregulated in SPRET/EiJ. Sequence analysis of all candidate genes revealed SNPs only in Pcsk2.
  
  Out of 18 SNPs one resulted in a phenylalanine (C57BL/6J) to leucine (SPRET/EiJ) amino acid substitution. This change is not predicted to alter protein function. Pcsk2 is considered the strongest candidate gene since it has a known role in metabolism. Other QTLs mapping near Bsbob include Gnf1 (81.4 cM) and Bfq1 (81 cM). Bsbob is also syntenic to a region on human Chromosome 20 where QTLs for body mass index havebeen mapped.
  
  A suggestive locus associated with epididymal white adipose tissue mass may be located in a 2.5 Mb interval distal to Bsbob. Congenic animals heterozygous for this region display significantly increased epididymal fat mass compared to animals of either homozygous genotype.