Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  19
• Reference
  J:109581 Clee SM, et al., Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus. Nat Genet. 2006 Jun;38(6):688-93
• ID
  MGI:3639691

Genes

Gene	Assay Type
T2dm2	visible phenotype
D19Mit70	PCR amplified length variant
Sorcs1	reported elsewhere

Notes

• Experiment
  Previously identified diabetes QTL T2dm2 (53 cM) on mouse Chromosome 19 was confirmed and further refined using interval specific congenic strain (ISCS) analysis. A 7 Mb region of chromosome 19 containing T2dm2 from 47.8 Mb - 54.8 Mb was transferred fromdiabetes-resistant strain C57BL/6J onto a diabetes-susceptible BTBR genetic background. Authors refer to this strain as 1339A. Obese 1339A congenic females displayed a 30% reduction in fasting plasma insulin levels compared to controls. In vivo insulin response was impaired (50% reduction following glucose challenge) and pancreatic islet cells exhibit loss of structural integrity in 1339A congenic females.
  
  A series of 11 subcongenic lines was derived from 1339A. 325 obese female animals from the subcongenic lines were analyzed for 31 microsatellite markers and SNPs spanning the T2dm2 locus. Significant linkage to reduced insulin secretion (35% reduction when homozygous for C57BL/6J alleles) mapped to approximately 50 Mb (LOD=9.05) from the end of Sorcs1exon 1 to D19Mit70 (51 cM). Sorcs1 is the only gene within the 7 Mb congenic region containing mutations resulting in coding sequence changes. A threonine to isoleucine substitution at amino acid 52 potentially produces 3 different Sorcs1 transcripts. Other non-conservative amino acid changes and Sorcs1 promoter polymorphisms were observed but reside outside the QTL linkage region. 1339A congenic animals exhibit 10-fold higher Sorcs1 mRNA expression in pancreatic islet cells compared to BTBR control animals. Other genes contained within the T2dm2 QTL interval do not exhibit mRNA expression differences between 1339A congenics and BTBR controls.