Mapping Data

Experiment

• Experiment
  TEXT
• Chromosome
  1
• Reference
  J:138216 Dokmanovic-Chouinard M, et al., Positional cloning of 'Lisch-Like', a candidate modifier of susceptibility to type 2 diabetes in mice. PLoS Genet. 2008 Jul;4(7):e1000137
• ID
  MGI:3814222

Genes

Gene	Assay Type
Ildr2	visible phenotype
D1Mit110	PCR amplified length variant

Notes

• Experiment
  Linkage analysis was performed on 404 obese (C57BL/6J x DBA/2J)F2 animals homozygous for Lep^ob to identify genetic loci associated with diabetes traits. Animals were phenotyped at 120-150 days of age. Parental strain C57BL/6J-Lep^ob is resistant to diabetes whereas DBA/2J-Lep^ob is susceptible to diabetes.
  
  Significant linkage mapped to 169.6 Mb on mouse Chromosome 1 near D1Mit110 with LOD>8. This locus displays linkage to fasting blood glucose, HbA1c and islet cell histology and is named Dbsm1 (diabetes susceptibility modifier 1). Dbsm1 exhibits modest interaction with a locus on mouse Chromosome 4 at 14 cM near D4Mit286 (P=0.008).
  
  Congenic and subcongenic line analysis refined the Dbsm1 interval to a 3.2 Mb region from 169.9 Mb (rs30708865) to 173.1 Mb (rs31547961). Male animals carrying DBA/2J-derived DNA at Dbsm1 on a C57BL/6J-Lep^ob genetic background display reduced beta-cell mass, impaired glucose tolerance, decreased plasma insulin levels, and increased fasting blood glucose levels on a CHOW diet up to 120 days of age. In addition, lean male animals carrying DBA/2J-derived DNA at the Dbsm1 interval on a C57BL/6J genetic background without the Leb^ob mutation display hyperglycemia when fed a high fat diet for 13 weeks.
  
  Fourteen potential candidate genes within the minimum congenic interval were evaluated by SNP analysis and/or mRNA expression assay using various tissues from B6.D2-Dbsm1^DBA/2J Leb^ob congenic animals. A gene named "Lisch-like" at 168.18 Mb (D1Ertd471e) displayed a 2- to4-fold expression difference between B6.D2-Dbsm1^DBA/2J Lep^ob congenic animals and control animals in the liver and other diabetes-relevant organs.
  
  A hypomorphic allele of Lisch-like generated by ENU mutagenesis on a C3HeB/FeJ genetic background results in reduced beta-cell replication rate in 14 day old animals. Mutant animals display reduced plasma insulin concentration at time of sexual maturation and male animals 50-days of age display increased glucose AUC in a glucose tolerance test.