Mapping Data

Experiment

• Experiment
  TEXT
• Chromosome
  5
• Reference
  J:143559 Chadt A, et al., Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet. 2008 Nov;40(11):1354-9
• ID
  MGI:3835792

Genes

Gene	Assay Type
Tbc1d1	visible phenotype
D5Mit82	PCR amplified length variant
D5Mit15	PCR amplified length variant
D5Mit290	PCR amplified length variant

Notes

• Experiment
  Nobq1 (New Zealand obese QTL 1) on mouse Chromosome 5 was confirmed using a recombinant congenic line carrying SJL/NBom-derived DNA from 53.6 Mb to 77.5 Mb on a C57BL/6JCrl genetic background. This line is designated B6.SJL-(D5Mit302-D5Mit307). SJL/NBom-derived alleles at Nobq1 confer decreased body weight and blood glucose levels in animals fed a high fat diet. A separate congenic line confirmed the effect of homozygous SJL/NBom-derived alleles at Nobq1 on lower body weight and decreased adipose tissue mass in animals fed a high fat diet. Increased lipid oxidation was also observed in congenic animals.
  
  Fine map analysis performed on F2 animals from a B6.SJL-(D5Mit302-D5Mit307) and NZO/HlBom intercross refined the Nobq1 interval to an 8 Mb region between D5Mit82 (36 cM; 58 Mb) and D5Mit15 (39 cM; 65.7 Mb). Nineteen genes are located in this interval, two of which display mRNA expression differences between lean SJL/NBom and obesity susceptible NZO/HlBom progenitor strains. Riken gene 2310045A20Rik at53.48 Mb is upregulated in brown fat tissue in SJL/NBom females and is upregulated in liver tissue in SJL/NBom males. Tbc1d1 at 64.5 Mb is precisely near the Nobq1 linkage peak (D5Mit290) and this gene is downregulated 70% in the skeletal muscle of SJL/NBomanimals.
  
  Sequence analysis of Tbc1d1 revealed a 7 base pair deletion in exon 18 that is specific to the SJL/NBom inbred strain. This frameshift mutation results in a loss of function truncated protein and is not present in SJL-related (SWR, FVB) andunrelated (B6, NZO, NZB, etc) strains. In addition, two recent human studies found an association between TBC1D1 SNPs and susceptibility to type 2 diabetes.